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1. Introduction

The retina originates in the neuroectodermal region and is derived from the anterior neural tube; thus, it is considered to be part of the central nervous system. The mature mammalian retina is classically divided into ten layers, which order from the inside to outside; the inner limiting membrane, nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, external limiting membrane, photoreceptor layer and retinal pigment epithelium. The retina contains neuronal elements identified as photoreceptors and horizontal, bipolar and amacrine cells and retinal ganglion cells (RGCs) (1,2). Comprising ~1% of all retinal cells, RGCs are the final output neurons of the retina (3). RGCs receive synaptic inputs from bipolar, amacrine and interplexiform cells, as well as from gap junctions. Their axons cross the retina and exit the eye via the optic disk, where they form the optic nerve, relaying information to the visual centers of the brain. Information received at the retinal level is conveyed to visual centers via discharge patterns of RGCs. Thus, the intrinsic membrane properties of RGCs are crucial in determining the methods by which visual information is transmitted to the brain (4). Discharge patterns of RGCs are primarily determined by the presence of ion channels, including sodium (Na+) and potassium (K+) ion channels. Of these ion channels, K+ channels are important in RGC development, neurite outgrowth, axon guidance and action potential and repetitive firing regulation (5,6).

A number of eye diseases, including glaucoma, ischemic optic neuropathy, retinal degeneration and trauma, may cause injury or the death of RGCs, and subsequently permanent visual dysfunction. The study of ion channels, particularly K+ channels in RGCs, may be beneficial in elucidating the pathophysiology of RGCs and exploring novel RGC protection strategies. In the past three decades, there has been considerable progression in research on the function of K+ channels in RGCs (7,8). The aim of the current review was to summarize the roles of K+ channels in RGC development, neurite outgrowth, axon guidance and the modulation of electrical properties.

2. Classification of K+ channels

There are several types of K+ channels, including voltage-gated K+ (Kv), Ca2+-activated K+ (KCa), inward-rectifier K+ (Kir), tandem-pore domain K+ (TASK; also named ‘leak’ K+) and ATP-sensitive K+ (KATP) channels (7,8). K+ channels are classified into three groups based on their predicted membrane topology; those with two, four and six transmembrane domains (TMDs; Fig 1). The first group, consisting of two TMDs, comprises Kir channels. The second group, consisting of four TMDs, comprises ‘leak’ K+ channels (known as two-pore channels) and the third group with six TMDs comprises Kv and KCa channels. Each of these groups is divided into families, which are further divided into subfamilies, the majority of which have several closely related members (8).

Figure 1 Classification of potassium ion channels. TMD, transmebrane domain; KATP, ATP-sensitive K+ channel; Kir, inward-rectifier channel; TASK, tandem-pore domain K+ channel; KV, voltage-gated K+ channel; EAG, ether-á-go-go channel; KCa, Ca2+-activated channel; BKCa, large conductance KCa channel; SKCa, small conductance KCa channel.

The first group has a predicted membrane topology of two TMDs (M1–M2) and a pore (P) domain; this group includes Kir and KATP channels. Currently, seven subfamilies (Kir1–7) have been identified, the majority of which form K+ channels with varying degrees of inward rectification when expressed in heterologous expression systems (8).

The second group contains four putative TMDs (M1–4) and two P domains (P1 and 2) (9,10) and are referred to as TASK channels. There are currently five members in this family (mechano-gated TREK, alkaline-activated TALK, calcium-activated TWIK, acid-inhibited TASK and halothane-inhibited THIK channels; Fig 1) (11–13), however, there is a possibility of new members being cloned in the future. The current responds to changes in the extracellular K+ concentration, as described by the Goldman-Hodgkin-Katz equation, thus these channels are also referred to as ‘leak’ K+ channels (9). A number of these channels may be extensively modulated by specific factors (e.g., arachidonic acid or pH) (14).

The third group contains six TMDs (S1–S6) with a conserved P (pore or H5) domain. When expressed in heterologous expression systems, Kv and/or KCa channels are formed. This group contains the Kv channel family (with eight subfamilies, Kv1–6, 8 and 9), as well as members of the ether-à-go-go (Eag) and KCa channel families (8).

3. Expression of K+ channels in RGCs

Biochemical, molecular and pharmacological studies have identified numerous types of K+ channels in RGCs, including Kir(15–17), KATP(18), TASK (19), Kv(6,15,20), Eag (21) and KCa channels (Table I) (22,23). Various subtypes of Kir channels have been confirmed to be expressed in RGCs in Xenopus laevis(15) and rats (16,17,22). Specific subunits of Kv channels have been observed to be expressed in RGCs in Xenopus laevis(6,15,24,25), goldfish (26), trout (27), mice (28–30,31), rats (20,32,33) and cats (34). Eag1 and Eag2 have been reported to be expressed in RGCs in rats (21) and cattle (35). Large-conductance KCa channels (BKCa) and small-conductance KCa channels (SKCa) have been identified to express RGCs in ferrets (36), trout (27), mice (37) and rats (22,23). Various subunits of K+ channels are expressed in RGCs with distinct subcellular localization. Chen et al(16) previously reported that Kir1.1 was mainly expressed in the axons of RGCs, and Kir2.1 and Kir2.3 were present in the somata of RGCs. Staining methods demonstrated that Kir3.1 was primarily present in an endoplasmic reticulum-like structure and Kir3.2 was expressed in the cytoplasm and the cytomembrane of somata, dendrites and axons of RGCs. Faint, sparse labeling for Kir3.3 was observed in the cytomembrane. Tian et al(17) reported marked staining of Kir2.1 in the cytoplasm and staining for Kir1.1, 2.3, 3.1, 3.2, 3.3 and 4.2 was predominantly observed on the cell membrane. Concentrated Kv1.1 and Kv1.3 staining was present in RGC somata, while Kv1.2 distribution was restricted, with intense staining in RGC axon fascicles (20,29). Jow and Jeng (21) observed the expression of Eag1 and Eag2 in the somata of rat RGCs.

Table I Potassium ion channels in retinal ganglion cells.

Table I

Potassium ion channels in retinal ganglion cells.

Classes of K+ channel	K+ channel	Species	Reference
Inward-rectifier K + channels	Kir1.1	Rat	16, 17
	Kir2.1	Xenopus laevis	15
		Rat	16, 17
	Kir2.3	Rat	16,17
	Kir3 (GIRK)	Rat	22
	Kir3.1	Rat	16, 17
	Kir3.2	Rat	16, 17
	Kir3.3	Rat	16, 17
	Kir4.2	Rat	17
	KATP	Rat	18
Tandem-pore domain K+ channels	TASK-2	Rat	19
Voltage-gated K+ channels	Kv	Mouse	28
		Cat	33
	Kv1.1	Xenopus laevis	15
		Rat	20, 31
	Kv1.2	Mouse	29
		Rat	20
	Kv1.3	Xenopus laevis	6
		Mouse	29
		Rat	20, 31
	Kv1.4	Mouse	29
	Kv1.5	Xenopus laevis	6
	Kv2.1	Mouse	29
	Kv3.1	Trout	27
		Rat	32
	Kv3.2	Rat	32
	Kv3.4	Xenopus laevis	6
	Kv4.2	Goldfish	26
		Xenopus laevis	6
		Mouse	29, 30, 37
	Kv4.3	Xenopus laevis	24, 25
	Eag1	Rat	21
		Bovine	34
	Eag2	Rat	21
		Bovine	34
Ca2+-activated K+ channels	SKCa	Ferret	35
		Rat	22, 23
	BKCa	Ferret	35
		Trout	27
		Mouse	36

[i] K_ir, inward-rectifier channel; GIRK, G-protein-coupled inwardly rectifying K⁺ channel; K_ATP, ATP-sensitive K⁺ channel; TASK, tandem-pore domain K⁺ channel; K_V, voltage-gated K⁺ channel; Eag, ether-á-go-go channel; BK_Ca, large conductance K_Ca channel; SK_Ca, small conductance K_Ca channel.

4. Effects of K+ channels on RGCs

RGCs function as output neurons in the retina, encoding visual signals by producing spikes with characteristic spatial and temporal patterns. The encoded signals are relayed to visual centers via RGC axons. As the most diverse group of ion channels, K+ channels play a key role in modulating the electrical properties of neurons (5,6).

5. Kir channels

Kir channels are characterized by inward rectification, which allows more current to flow inward than outward via the channels (38). These channels are important for regulating neuronal signaling and membrane excitability (16,39–41). Kir channels are important in the maintenance of resting membrane potentials, thereby controlling the excitability of neurons (42). Kir channels are characterized by an increasing conductance under hyperpolarization and a decreasing conductance under depolarization (43). There are seven Kir subfamilies (Kir1–7) (44), including ATP-regulated (Kir1), classical (Kir2) and G-protein-coupled (Kir3; GIRK). These subfamilies have varying properties and kinetics, mediating distinct physiological functions (45). It has previously been reported that GIRK channels containing Kir3.2 and 3.3 subunits mediate the hyperpolarization and decrease in the firing rate of rat locus coeruleus neurons caused by acute opioid administration (46). Activation of Kir channels serves as an underlying mechanism for improved RGC survival (43). Adenosine-induced hyperpolarization of RGCs is produced via the activation of A1 receptors, initiating a signaling cascade that activates GIRK and SKCa channels. This represents a novel mechanism of adenosine-mediated neuromodulation that may contribute to the regulation of RGC activity (22). Flupirtine, a drug approved for patients suffering from chronic pain, may protect RGCs from degeneration in a non-inflammatory animal model of optic nerve transection. It has been verified through patch-clamp studies that the activation of Kir channels is involved in flupirtine-mediated neuroprotection (47).

6. KATP channels

KATP channels belong to the family of Kir channels, and are composed of pore-forming units and a sulfonylurea binding site (48). These channels are located in the plasma membrane, as well as in the mitochondrial inner membranes (43,49,50). Mitochondria supply energy to the cell via the synthesis of ATP. Respiring mitochondria transport H+ into the cytoplasm, forming a transmembrane potential and pH gradient at the mitochondrial membrane. An influx of K+, due to the opening of mitochondrial KATP channels, decreases the electrical gradient, but not the pH gradient, at the mitochondrial membrane. Consequently, mitochondria no longer have to maintain two gradients and therefore become more resistant to stress by conserving energy (48,51). This indicates that KATP channels may be involved in RGC survival and neuroprotection. A number of studies have shown that KATP channels are important in enhancing retinal resistance against ischemic insult (18,52,53). Retinal ischemic injury induces retinal neuron cell death by excitotoxicity. In excitotoxic injury, increased glutamate causes the continuous opening of NMDA or kainate channels, damaging the retinal ion balance. The disturbed ionic environment is deleterious to retinal neurons and leads to cell death. ATP depletion leads to an opening of plasmalemmal channels, which hyperpolarizes the cell membrane in states of energy deficiency or ischemia (54). Yamauchi et al(52) previously reported that the opening of mitochondrial KATP channels may inhibit glutamate. The opening of K+ channels induces the reduction of K+ ion levels in the cytoplasm, which is accompanied by an increase in ischemic tolerance, mimicking ischemic preconditioning (55). This has been hypothesized to function in a similar manner to the way that low levels of K+ ions inhibit or delay neuronal cell toxicity by Ca2+ influx in excitotoxicity (56). A number of potent KATP-channel openers, including KR-31378 and gabapentin-lactam, exhibit RGC neuroprotection by regulating ion balance during excitotoxicity (56,57). KATP channel agonists may prevent ischemia-induced expression of the immediate early genes, c-fos and c-jun (58). In addition, KATP channels are essential for cerebral ischemic preconditioning (59–61). Early ischemic preconditioning has been demonstrated in the rat retina, and KATP channel openers mimic the effect of ischemic preconditioning (59). The activation of KATP channels following a sublethal ischemic stimulus may involve adenosine/adenosine receptors, as KATP channels are localized in close proximity to adenosine A1 receptors (62). A release of endogenous adenosine from the retina following K+ depolarization or ischemic insult has been reported (63,64). It is therefore conceivable that adenosine formed from the breakdown of ATP may be released during the initial ischemia and indirectly activates KATP channels via the G-protein pathway following binding to the adenosine A1 receptor (65). Sakamoto et al(53) observed that the stimulation of adenosine receptors, opening of KATP channels and activation of protein kinase C may be involved in the underlying protective mechanisms of early ischemic preconditioning.

7. TASK channels

TASK channels belong to the four putative TMD and two pore domain channels (13). These channels are divided into three subtypes, TASK-1, −2 and −3. TASK channels are distinguished from other family members of K+ channels due to their sensitivities to changes in extracellular pH. Although they have varying ranges of pH sensitivity, these channels are activated by extracellular alkaline pH and inhibited by acidic pH (19). TASK channels are not all voltage-gated and are resistant to conventional K+ channel blockers. In addition, these channels have been hypothesized to contribute to the regulation of resting membrane potentials and firing patterns of neurons (11,13). TASK-2 is expressed in RGCs, indicating that TASK-2 may be involved in the regulation of resting membrane potentials and firing patterns of RGCs.

8. Kv channels

Kv channels contain eight potassium channel subfamilies (Kv1–6, 8 and 9). All the electrically active Kv channel subfamilies are represented in the adult rodent retina in spatially restricted patterns (29,66,67). The coordinated expression of Kv channels is of key importance for the maturation of membrane excitability and electrical signaling behavior in the retina. These channels determine the resting membrane potential of retinal neurons, particularly RGCs, modulating their intrinsic firing properties (68) and regulating neuronal differentiation processes (24). There are three aspects of the effect of Kv channels on RGCs.

RGC electrical activity

Kv currents are important regulators of cellular excitability, functioning to modulate the amplitude, duration and frequency of action potentials and subthreshold depolarizations. Altering Kv channel function is useful for identifying the cellular processes that are regulated by excitability (69). Kv channels carry outward currents that repolarize the membrane in response to action potentials or spontaneous depolarizations. Therefore, Kv channels are critical for determining the shape of the action potential, the time course and extent of the hyperpolarization following a spike, return to resting potential, the delay to spike onset and in regulating repetitive firing (5,44,70,71). In RGCs, Kv channels exhibit a distinct subcellular localization pattern in the axon, thereby shaping the firing patterns of action potentials (72). Kv1.3 channels produce a slowly inactivating current, whereas Kv1.1 and 1.2 produce currents with fast or slow inactivation, depending on accessory molecules (73). Kuznetsov et al(33) observed that Kv3.1/3.2 channels underlie the fast firing of rat RGCs and provide, at a given firing frequency, a 1.8-fold restriction of Ca2+ influx, which protects the cells from its cytotoxic action.

RGC development

A number of studies have indicated that Kv channels have important and varied roles in the development of neuronal cell types, and they have been implicated in numerous processes, including cell proliferation or differentiation, neurite outgrowth and axon guidance. Pollock et al(6) revealed that the retinal expression patterns of different Kv channels have various roles in retinal development. Kv1.3, 1.5, 3.4 and 4.2 channels became restricted to postmitotic retinal cells and/or synaptic layers, indicating additional roles for these channels in cell differentiation and synaptogenesis. The restricted and transient nature of Kv4.2 protein expression in RGCs is particularly intriguing, as it implicates the Kv channel in the differentiation of a specific RGC subtype. The presence of Kv1.3 channels in axons indicates that they may be involved in the myelination of the optic nerve. Kv1.3, 1.5 and 3.4 subunits continue to be expressed by RGCs beyond the time the visual system first becomes functional, indicating that they are eventually involved in the regulation of electrical activity (6). It is proposed that these Kv channels, through their control of membrane potential, regulate the downstream signaling of axon growth and guidance cues (74). Membrane excitability regulates the earliest differentiation of RGC dendritic arbors (15), while key regulators of membrane excitability are Kv channels (44,71). This indicates that Kv may regulate the differentiation of RGC dendritic arbors. McFarlane and Pollock (24) observed that RGCs and their growth cones express Kv channels during progression to the midbrain target, the optic tectum. It was also observed that the blockade of Kv channels using 4-aminopyridine, a Kv channel blocker, inhibited RGC axon extension and caused the aberrant routing of numerous RGC fibers. Inhibiting Kv channels affects the ability of RGC axons to extend in culture and causes extension and pathfinding defects of the axons in vivo. These observations indicate that Kv channel activity regulates the guidance of growing axons of RGCs. Pollock et al(75) reported that the chemorepellent fibroblast growth factor-2 repulsed RGC growth cones in the presence of 4-aminopyridine, but not tetraethylammonium, indicating that tetraethylammonium- and 4-aminopyridine-sensitive Kv channels differ in the manner by which they regulate the response of RGC axons to extension and guidance cues. Qu et al(30) noted that Kv4.2-mediated currents were important for development in a subset of RGCs, particularly around postnatal day 10 as the bipolar cells mature. In addition, the majority of mouse and cat RGCs express Kv currents soon after birth, before the cells have the ability to generate spontaneous action potentials (28,33).

The regulation of intracellular calcium ([Ca2+]i) appears to be a particularly attractive function for Kv channels, since resting [Ca2+]i and dynamic changes in [Ca2+]i are important for regulating the response of the growth cone to extrinsic cues (76–78). In growth cones, Kv channel activity may function to modulate [Ca2+]i by regulating the membrane potential and opening voltage-gated Ca2+ channels. Maruoka et al(79) and Petrecca et al(80) observed that Kv1.5 and 4.2 channels coimmunoprecipitated with the cytoskeletal components of α-actinin-2 and filamin, respectively, indicating the possibility of specific Kv channels functioning directly or indirectly in the reorganization of the cytoskeleton in response to extrinsic cues.

RGC protection

Apoptosis in several cell types is accompanied by increased K+ currents, the depletion of cytoplasmic K+ and cell shrinkage (81–84). This ‘apoptotic volume decrease’ precedes mitochondrial depolarization, apoptosome formation and cell fragmentation, and is considered to be a triggering event (81–84). The volume decrease of apoptotic cells occurs through the channel- and transporter-mediated efflux of osmolytes, particularly K+ and chloride ions. This ion efflux creates an osmotic gradient that draws water out of the cells (85–87). The decrease in cytoplasmic K+ concentration may activate molecules in the apoptotic cascade. Consequently, one experimental strategy has been to target K+ channels. An increasing number of studies support the hypothesis that Kv channels are involved in the protection of RGCs. Kv1.1 and Kv1.3 channels contribute to cell-autonomous death of RGCs through various components of the apoptotic machinery (20). Kv1.1 depletion increases the anti-apoptotic gene, Bcl-xL. By contrast Kv1.3 depletion reduces the pro-apoptotic genes, caspase-3, caspase-9 and Bad (20). It has been reported that Kv contributions depend on their location. Kv1.1 and 1.3 are highly expressed in RGC somata and have the greatest effect on cell survival, whereas the contribution of the predominantly axonal Kv1.2 channel is limited (20). By contrast, Kv channels are functionally linked to RGC degeneration indirectly via non-neuronal cells, most likely by blocking Kv1.3 channels in microglia (31,88–90). The Kv1.3 channel is highly expressed in microglia and contributes to microglial activation and neurotoxicity (91). Utilizing the optic nerve transection model, Koeberle et al(32) reported the following observations: (i) Following optic nerve transection, intraocular injection of agitoxin-2, a potent blocker of Kv1.3 channels, reduced microglial activation and the expression of several inflammatory genes in the damaged retina, which indicated that Kv channels contribute to inflammation in the adult retina in vivo; (ii) the retinal expression of several growth factors was upregulated following axotomy. Intraocular injection of margatoxin, a blocker of Kv1.3 channels, increased retinal b-FGF. By contrast, RGC-specific depletion of Kv1.3 from RGCs decreased GDNF and b-FGF levels. Agitoxin-2 injection did not affect growth factor levels; (iii) injecting agitoxin-2 increased c-Fos, TGFβ, IL-1β, IL-1ra and TNFα beyond any effects of Kv1.1 or Kv1.3 channel knockdown in RGCs; and (iv) combining siRNA-mediated knockdown of Kv1.1 or 1.3 with intraocular injection of agitoxin-2 or margatoxin provided increased RGC rescue, with up to 55% of RGCs surviving at day 14 following optic nerve transection (31). In addition, as the Kv1.3 channel is important for the activation of T lymphocytes, it is also possible that this channel is involved in immune-mediated damage in the retina (92).

9. Eag channels

The Eag channel was the first reported member of the Eag family of voltage-gated K+ channels (93). In mammals, two Eag channel subunit isoforms have been identified, Eag1 and Eag2, sharing ~70% identity in amino acid sequence (94–96). Jow and Jeng (21) observed that Eag1 channels are localized at the dendrites and somata of RGCs, and Eag2 channels are localized at the somata of RGCs. Eag1 and Eag2 channels have also been identified to express RGCs in cattle (34). The widespread expression of Eag1 channels in the somatodendritic compartment indicates that these channels may contribute to dendritic repolarization during excitatory postsynaptic potentials and to the attenuation of the back propagation of action potentials. Thus, Eag1 channels are critical in regulating electrical coupling between dendrites and cell bodies in RGCs (21). In addition, Eag channels are involved in the formation of IKx channels and may contribute to the dark current in the rod inner segment (34).

10. KCa channels

Single channel studies have revealed several types of calcium-activated potassium channels, which may be divided into two distinct groups based on their pharmacological and biophysical properties, BKCa and SKCa. BKCa channels, which may be blocked by charybdotoxin (CTX), have a high unitary conductance and exhibit sensitivity to voltage and submicromolar concentrations of CTX (97). The current passing through these channels has been implicated in action potential repolarization and fast hyperpolarization following the spike (98). By contrast, SKCa channels have a markedly lower unitary conductance, are voltage- and CTX-insensitive and are activated by nanomolar concentrations of calcium (97). The current flowing through these channels is sensitive to apamin, a SKCa channel blocker, and has been shown to underlie the slow after-hyperpolarization that is responsible for action potential frequency adaptation in a number of cells (99,100). KCa currents have been reported to be important in the regulation of neuronal activity. In particular, these currents have been shown to contribute towards the repolarizing phase of the action potential (98), control the repetitive discharge of spikes (101–103) and are involved in various forms of oscillatory membrane behavior (104).

BKCa and SKCa channels are located in RGCs (3,35,105). KCa channels contribute to repetitive firing in RGCs (105), and blocking KCa channels has been shown to increase the current-evoked firing rate of RGCs in ferret retinas (35). Whole-cell recordings from isolated and intact RGCs revealed that conductances regulate the frequency of spike discharges in response to maintained depolarizations. Activation of these channels leads to an increase in the time to spike threshold and in the hyperpolarization following the spike, decreasing the rate of sustained discharges (35). Wang et al(106) revealed that apamin induced low-frequency bursts of a relatively long duration, a pattern similar to that observed in developing RGCs. By contrast, CTX induced high-frequency bursts of a short duration that were periodic; these observations indicate that the modulation of KCa conductances provides an effective means for affecting the spontaneous discharge patterns of RGCs. In addition, firing patterns were evident following blockade of the small conductance and resembled the spontaneous discharges noted during development, indicating a possible link between the functional state of KCa conductances and the spontaneous discharges manifested by immature RGCs (106). Utilizing patch-clamp recordings in mouse RGCs, Nemargut et al(37) observed that during dark adaptation, the blockage of BKCa channels increased the spontaneous excitatory postsynaptic currents (EPSCs) and light-evoked on-EPSCs, while it decreased the light-evoked off-inhibitory postsynaptic currents (IPSCs). However, under light adaptation, it decreased the light-evoked on-EPSCs, the spontaneous IPSCs and the light-evoked on- and off-IPSCs. The blockage of BKCa channels significantly altered the outputs of RGCs by changing their light-evoked responses into a bursting pattern and increasing the light-evoked depolarization of the membrane potentials, while it did not significantly change the peak firing rates of light-evoked responses (36). These observations indicate that BKCa channels play various roles in mediating visual signals in the retina under different ambient light conditions.

11. Conclusions

The discharge patterns of RGCs are primarily determined by the presence of ion channels. As the most diverse group of ion channels, K+ channels are key in modulating the electrical properties of RGCs. Biochemical, molecular and pharmacological studies have identified numerous types of K+ channels in RGCs, including Kir, KATP, TASK, Kv, Eag and KCa. Kir channels are important in maintaining the resting membrane potential and modulating RGC excitability. KATP channels are involved in RGC survival and neuroprotection. TASK channels are considered to contribute to the regulation of resting membrane potentials and the firing patterns of RGCs. Kv channels are important regulators of cellular excitability, functioning to modulate the amplitude, duration and frequency of action potentials and subthreshold depolarizations. Kv channels are important in RGC development and protection. Eag channels may contribute to dendritic repolarization during excitatory postsynaptic potentials and to the attenuation of the back propagation of action potentials. KCa channels have been observed to contribute to repetitive firing in RGCs. Considering these important roles of K+ channels on RGCs, the study of K+ channels may be conducive to elucidating the pathophysiology of RGCs and to explore new RGC protection strategies.

Acknowledgements

This study was funded by the Shanghai Leading Academic Discipline Project (no. S30205) and the Shanghai ‘Science and Technology Innovation Action Plan’ Basic Research Key Project (nos. 11JC1407700 and 11JC1407701).

References