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Functional roles of voltage-Gated Calcium Channels in retinal bipolar cells
Abstract
Retinal bipolar cells, the second order neurons in the retina, relay visual information from photoreceptors to retinal third order neurons, amacrine and ganglion cells. Bipolar cells respond to light usually with graded membrane potentials. Bipolar cells express both low voltage-gated T-type and high-voltage-gated L-type calcium channels. In the CNS, voltage-gated calcium channels have been known to play an important role in regulating membrane excitation as well as triggering neurotransmitter release at presynaptic terminals. This review emphasizes on the functional roles of L- and T-type Ca2+ channels in retinal bipolar cells.
I. Bipolar cells transfer information from photoreceptors to ganglion cells
Retinas are composed of three layers of nerve cell bodies and two layers of synapse contacts. The outer nuclear layer contains cell bodies of the rods and cones photoreceptors, the inner nuclear layer contains cell bodies of the bipolar, horizontal and amacrine cells and the ganglion cell layer contains cell bodies of ganglion cells and displaced amacrine cells. Between these nerve cell layers are two plexiform layers where synaptic contacts occur (webvision). Bipolar cells transfer light signals from rods or cones photoreceptors to ganglion cells. There are two basic types of bipolar cells presenting in the mammalian retina: cone bipolar cell (CBs) and rod bipolar cells (RBs) which mainly receive cone and rod inputs, respectively. There are nine types of cone bipolar cells but only one type of rod bipolar cell (Masland RH,2001).
Functionally, bipolar cells can be divided into ON- and OFF-cells based on based on their response polarity to light. All rod bipolar cells are ON-cells. Metabotropic glutamate receptors locate at the dendrites of ON-type bipolar cells. Ionotropic glutamate receptors locate at the dendrites of OFF-type bipolar cells. In this way, ON- and OFF-type bipolar cells respond to light signal differently: ON- bipolar cells depolarize in response to light while OFF- bipolar cells hyperpolarizing (Euler T, 1995, 1999).Graded membrane polarizations control the rate of transmitter release on bipolar cell terminals through voltage-gated calcium channel.
II. Voltage-gated calcium channels
Voltage-gated calcium channels are heterotrimeric protein complex. Voltage-gated calcium channels have a pore-forming α1 subunit associating with other ancillary subunits, such as β, α2 and δ subunits (ReuterH, 1996). The α1 subunit’s structure is analogous to that of voltage-gated sodium channels. The α1 subunits undertake most of the pharmacological and electrophysiological properties of the channel, but the accessory subunits associate with the channel and alter its function properties (ReuterH, 1996).
Voltage-gated calcium channels have been classified into three main classes: Cav1 (L-type), Cav2 (P/Q-, N-, R-types), and Cav3 (T-type) by their electrophysiological and pharmacological properties (Edward Perez-Reyes, 2003). Tsien et al. extended the Ca2+ channels classification that these channels are called T-type for transient, L-type for long-lasting, and N-type for neither T- nor L-type (Tsien, 1985). In addition, Ca2+ channels found in the retina include all known mammalian Ca2+ channel subtypes (Miller RJ., 2001). However, in previous study, only L- and T-type Ca2+ channels are proved to be expressed on bipolar cells in distinct cellular compartments (Kaneko A, 1991; Pan Z-H. 2001).
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HVA(High voltage activated )
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Cav1
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Cav1.1, α1S, L-type
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Cav1.2, α1C, L-type
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Cav1.3, α1D, L-type
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Cav1.4, α1F, L-type
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Cav2
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Cav2.1, α1A, P/Q-type
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Cav2.2, α1B, N-type
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Cav2.3, α1E, R-type
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LVA(Low voltage activated)
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Cav3
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Cav3.1, α1G, T-type
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Cav3.2, α1H, T-type
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Cav3.3, α1I, T-type
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Fig.1. Voltage-gated calcium channels (modified from ref.5)
III. Mechanism of transmitter release from photoreceptor and bipolar cell terminals
Rod and cone photoreceptors and bipolar cells usually do not produce action potentials. To continue releasing transmitter, photoreceptors and bipolar cells use a specialized structure, called synaptic ribbon. Ribbon is a membranous structure above the terminal. A large number of small clear-core synaptic vesicles are tethered by protein filaments to the synaptic ribbon (Dowling, 1987). The synaptic vesicles near the base of the ribbon are continuing fusing with cell membrane. So the neurotransmitter, glutamate, can be released continuingly into the invagination of terminals, in a calcium-dependent manner.
This transmitter vesicle fusion depends on Ca2+ influx through Ca2+ channels. In dark condition, photoreceptors are at resting potential of -40mV (Schneeweis, D.M. 1999) and membrane potentials of bipolar cells are believed to be around -70 to -20 mV (Bean BP, 1985 ; Simon et al., 1975; Ashmore and Falk, 1980; Ashmore and Copen- hagen, 1983; Saito and Kaneko, 1983). Voltage-gated Ca2+ channels can sense the transmembrane potential change about 1 mV at the synaptic terminals; regulate calcium influx into synaptic terminals. Synaptotagmin detect the concentration of calcium molecules; determine the rate of transmitter vesicle merging and transmitter release (Ruth Heidelberger, 2005). A depolarization causes an increase in transmitter releasing and hyperpolarization causes a decrease. In photoreceptors, L-type Ca2+ channels are thought to contribute to transmitter release. In bipolar cells, both L- and T-type Ca2+ channels may mediate synaptic release (see rev. by Ruth Heidelberger, 2005). Pan et al. observed a broad group of cone bipolar cells with prominent T-type Ca2+ currents (T-rich) and another groupwith prominent L-type Ca2+ currents (L-rich) (Hu, 2009). Diverse expressed voltage-dependent membrane channels may contributeto the multiple physiological properties of bipolar cells for segregatingvisual information into parallel pathways.
Fig.2. Ribbon structure of bipolar cell terminals (Jacques I Wadiche, 2006)
IV. L-type Ca2+ channels mediate transmitter release in the retina
4.1. α1F Ca2+ channels mutation in rod photoreceptor cells can cause night blindness
A member of the L-type family of calcium channels, α1F calcium channel, was discovered as the genetic locus of incomplete congenital stationary night blindness (CSNB2) (N. Torben Bech-Hansen, 1998).CSNB is a recessive non-progressive retinal disorder characterized by night blindness and decreased visual acuity et al (N. Torben Bech-Hansen, 1998). CSNB patients have a loss-of-function mutation on α1F calcium channels in rod photoreceptor cells.
In dark conditions, photoreceptors are at resting potential of -40mV (Schneeweis, D.M. 1999).At this membrane potential, α1F calcium channel are activated and constant calcium current enters into photoreceptor synaptic terminal. Light induce hyperpolarization in photoreceptor membrane, close α1F calcium channel, and the release of glutamate is reduced. A single photon can produce about 1 mV change in rod photoreceptor, and this change can be sensed by α1F calcium channels (Schneeweis, D.M. 1995).So in CSNB patient, the abnormal α1F calcium channel can’t sense the small membrane potential change and the light signal can’t be transfer to the second-order retina neuron, bipolar cells (N. Torben Bech-Hansen, 1998).
4.2. L-type Ca2+ channels mediate transmitter release in bipolar cells
Based on previous study on Mb1 bipolar cells in goldfish, transmitter release is thought to be mediate exclusively by high-voltage-activated (HVA) Ca2+ channels (Tachibana, M., 1993; Corey et al., 1984; Wilkinson and Barnes, 1996; Schmitz and Witkovsky, 1997; Heidelberger and Matthews, 1992; but see also Pan et al., 2001). However, Pan et al. report that in retinal bipolar cells, low-voltage-activated (LVA) Ca2+ channels also can mediate neurotransmitter release (Pan et al., 2001). The L-type Ca2+ channels in mammalian rod bipolar cells have been proved to be localized only at the axon terminal (Pan & Lipton 1995; Satoh et al., 1998; Protti & Llano, 1998; Hartveit, 1999). However, the molecular composition of L-type Ca2+ channels in different bipolar cells remains unknown.
The L-type Ca2+ currents were activated at a higher membrane potential (near -40 to -30 mV), and they reached their peak around -20 or -10 mV (Hu, 2009).
V. The role of T-type Ca2+ channels in the retinal bipolar cells
Previous study about voltage-gated calcium channels were mainly done on Mb1 bipolar cells in the goldfish. And in the goldfish, only L-type calcium channels are expressed. However, in mammalian bipolar cells, both L-type and T-type calcium channels are expressed (Pan, 2000).
Comparing with HVA Ca2+ channels, T-type channels are characterized by their activation at lower voltages, faster inactivation, slower deactivation, and smaller conductance of Ba2+ (Perez-Reyes, 2003). Low-voltage-activated T-type Ca2+ channels have been known to play a major role in generating the spontaneous activity in a wide variety of neurons in the central nervous system (CNS) (Huguenard, 1996). The T-type Ca2+ currents were activated at a membrane potential near -60 mV, and they reached their peak around -40 mV (Hu, 2009).
Pan et al.’s study demonstrates that T-type Ca2+ channels are expressed in bipolar cell with single-cell RT-PCR (Pan et al., 2001). For rod bipolar cells in the rat and mouse, previous studieshave shown that the L-type Ca2+ channels localize to the axon terminals (Hartveit, 1997; de la Villa, et al., 1998; Pan, 2000), whereas the T-type Ca2+ channels are located both in the soma and at the axon terminals (Pan et al., 2001).T-type Ca2+ currents not only can be recorded on bipolar cell terminals, but could also directly trigger transmitter vesicle fusion and transmitter release with the measurement of capacitance increase (Pan et al., 2001).
Conclusion
Current evidence suggests that neurotransmitter release in mammalian bipolar cells is mediated by both L-type and T-type Ca2+ channels. L-type and T-type calcium channels need different conditions to activate. So in the physiological conditions, L-type and T-type calcium channels play different roles in mediating transmitter release. Specifically, Neurotransmitter release in response to modest depolarizations (-30 mV~-40 mV) is mediated predominantly by T-type Ca2+ channels, whereas release in response to stronger depolarizations in most bipolar cells involves both T- and L-type (-10mV). In addition, the T- and L-rich cone bipolar cells are different morphologically. The soma size of the L-rich cone bipolar cells appeared to be larger in general than that of the T-rich cone bipolar cells. Consistently, these two cell groups differed in whole-cell capacitance values (Hu, 2009).
Nowadays, the study about L-type and T-type calcium channels using specific agonists and antagonists. Recent advance in genetics techniques provide new tools to further elucidate functional roles of calcium channels in the CNS, including retinal bipolar cells. In particular, multiple lines of L-type and T-type calcium channels knockout mice or conditioning knockout mice are now available.
However, the function of differentiation expressing of T-type and L-type Ca2+ channels in cone bipolar cells is still unknown. Concerning with the functions of cone bipolar cells, cone bipolar cells are further divided into ON- and OFF-types on the basis of their response to light (Werblin & Dowling, 1969). Furthermore, the sustained and transient responses in the retina have been reported to originate in bipolar cells (Awatramani & Slaughter, 2000). It would be interesting for future studies to determine whether these two groups of bipolar cells (T- and L-rich) correspond to different functional types of cone bipolar cells.
Reference
2. Ashmore, J.F., and Copenhagen, D.R. (1983). An analysis of transmission from cones to hyperpolarizing bipolar cells in the retina of the turtle. J. Physiol. 340, 569–597.
3. Ashmore, J.F., and Falk, G. (1980). Response of rod bipolar cells in the dark-adapted retina of the dogfish, scyliorhinus canicula. J. Physiol. 300, 115–150.
4. BEAN BP. Two kinds of calcium channels in canine atrial cells. Differences in kinetics, selectivity, and pharmacology. J Gen Physiol 86: 1–30, 1985.
5. Corey DP, Dubinsky JM, Schwartz EA. The calcium current in inner segments of rods from the salamander (Ambystoma tigrinum) retina. J Physiol 1984;354:557–575.
6. Dowling, J.E., 1987. The Retina: an Approachable Part of the Brain. Belknap Press, Cambridge, MA.
7. CAIPING HU, ANDING BI, AND ZHUO-HUA PAN Differential expression of three T-type calcium channels in retinal bipolar cells in rats Visual Neuroscience (2009), 26, 177–187.
8. Huguenard, J.R. (1996). Low-threshold calcium currents in central nervous system neurons. Annual Review of Physiology 58, 329–348.
9. Masland RH The fundamental plan of the retina. Nat Neurosci4:877– 886. 2001
10.Euler T, Wa¨ ssle H. Immunocytochemical identification of cone bipolar cells in the rat retina. J Comp Neurol 361:461–478. 1995.
11.Euler T, Schneider H, Wa¨ ssle H. Glutamate responses of bipolar cells in a slice preparation of the rat retina. J Neurosci 16:2934–2944. 1996.
12.Edward Perez-Reyes Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels Physiol Rev 83:117-161, 2003.
13.Heidelberger R, Matthews G. Calcium influx and calcium current in single synaptic terminals of goldfish retinal bipolar neurons. J Physiol (Lond) 1992;447:235–256.
14.Miller RJ. Rocking and rolling with Ca2+ channels. Trends Neurosci. 24: 445-449. 2001.
15.Kaneko A, Suzuki S, Pinto LH et al. Membrane currents and pharmacology of retinal bipolar cells: a comparative study on goldfish and mouse. Comp Biochem Physiol C 98:115-127.1991.
16.Pan Z-H. Differential Expression of High- and Two Types of Low-Voltage–Activated Calcium Currents in Rod and Cone Bipolar Cells of the Rat Retina J Neurophysiol 83:513-527, 2000.
17.Pan ZH, Hu HJ, Perring P, Andrade R. T-type Ca(2+) channels mediate neurotransmitter release in retinal bipolar cells. Neuron 2001;32:89–98.
18.Pan, Z.-H. & Lipton, S.A. (1995). Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals. Journal of Neuroscience 15, 2668–2679.
19.Jacques I Wadiche & Henrique von Gersdorff Long-distance signaling via presynaptic glutamate transporters Nature Neuroscience-9, 1352 -1353 .2006.
20. N. Torben Bech-Hansen et al. Loss-of-function mutations in a calcium-channel a1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness nature genetics volume 19 july .1998.
21.Satoh, H., Aoki, K., Watanabe, S.-H. & Kaneko, A. L-type calcium channels in the axon terminal of mouse bipolar cells. Neuroreport 9, 2161–2165. (1998)
22.Schmitz Y, Witkovsky P. Dependence of photoreceptor glutamate release on a dihydropyridine-sensitive calcium channel. Neuroscience 1997;78:1209–1216.
23.Schneeweis, D.M. Schnapf, J.L. The photovoltage of macaque cone photoreceptors: adaptation, noise, and kinetics. Journal of Neuroscience 19,1203-1216 1999
24.Schneeweis, D.M. Schnapf, J.L. Photovoltage of rods and cones in macaque retina. Science 268,153-1056, 1995
25.Saito, T., and Kaneko, A. (1983). Ionic mechanisms underlying the responses of OFF-center bipolar cells in the carp retina I: studies of responses evoked by light. J. Gen. Physiol. 81, 589–601.
26.Simon, E.J., Lamb, T.D., and Hodgkin, A.L. (1975). Spontaneous voltage fluctuations in retinal cones and bipolar cells. Nature 256, 661–662.
27.Reuter, H. Diversity and function of presynaptic calcium channels in the brain. Curent Opinions in Neurobiology 6,331-337 1996
28.Ruth Heidelberger, Synaptic transmission at retinal ribbon synapses Prog Retin Eye Res. Nov 24(6): 682–720. 2005
29.Tachibana, M., Okada, T., Arimura, T., Kobayashi, K. & Piccolino, M. (1993). Dihydropyridine-sensitive calcium current mediates neurotransmitter release from bipolar cells of the goldfish retina. Journal of Neuroscience 13, 2898–2909.
30.NOWYCKY MC, FOX AP, AND TSIEN RW. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 316: 440–443, 1985.
31.Wilkinson MF, Barnes S. The dihydropyridine-sensitive calcium channel subtype in cone photoreceptors. J Gen Physiol 1996;197:621–630.
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