Voltage-Gated Channels and Calcium Homeostasis in Mammalian Rod Photoreceptors

Abstract

. Voltage-gated channels and calcium homeostasis in mammalian rod photoreceptors. J Neurophysiol 93: 1468 -1475, 2005. First published October 13, 2004; doi:10.1152/jn.00874.2004. Recent reports on rod photoreceptor neuroprotection by Ca 2ϩ channel blockers have pointed out the need to assess the effect of these blockers on mammalian rods. However, in mammals, rod electrophysiological characterization has been hampered by the small size of these photoreceptors, which were instead extensively studied in nonmammalian vertebrates. To further characterize ionic conductances and to assess the pharmacology of Ca 2ϩ channels in mammalian rods, freshly dissociated pig rod photoreceptors were recorded with the whole cell patch-clamp technique. Rod cells expressed 1) a hyperpolarization-activated inward-rectifying conductance (I h ) sensitive to external Cs ϩ ; 2) a sustained outward K ϩ current (I K ) sensitive to tetraethylammonium; 3) a sustained voltage-gated Ca 2ϩ current (I Ca ) sensitive to benzothiazepine (diltiazem) and phenylalkylamine (verapamil) derivatives; 4) a Ca 2ϩ -activated Cl Ϫ current (I Cl(Ca) ); and 5) a plasma membrane Ca 2ϩ -ATPase. The Ca 2ϩ current showed a range of activation from positive potentials to -60 mV with a maximum between -30 and -20 mV. In contrast to other L-type Ca 2ϩ channels, rod Ca 2ϩ channels were blocked at similar and relatively high concentrations by the diltiazem isomers and verapamil. The biphasic dose-response for D-diltiazem confirmed the low sensitivity of Ca 2ϩ channels for the molecule. The ATPase, which was localized at the axon terminal, was found to contribute to Ca 2ϩ extrusion. These results suggest that the electrophysiological features of rod photoreceptors had been preserved during evolution from nonmammalian vertebrates to mammals. This work indicates further that mammalian rods express nonclassic L-type Ca 2ϩ channels, showing a low sensitivity to the diltiazem isomers used in neuroprotective studies.

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

“…The stimulation concept remains valid if one assumes different ion channel distribution in the anode-and cathode-facing membranes, respectively. The photoreceptor terminals contain a variety of voltage-gated channels (Cia et al 2005) that control the release of the excitatory neurotransmitter glutamate. If only bipolar cells are targeted by an electrical stimulus (Figs.…”

Alternative Splicing at C Terminus of CaV1.4 Calcium Channel Modulates Calcium-dependent Inactivation, Activation Potential, and Current Density

“…This posed a problem because rod photoreceptors hyperpolarize upon activation by light, apparently implying that in the normal operating range of the rod photoreceptor membrane potential Ca V 1.4 channels are minimally activated or not at all. Also, when native calcium currents in the rod photoreceptor were measured, they could be evoked at ϳ30 mV more hyperpolarized potentials than that obtained from cultured cells expressing cloned full-length Ca V 1.4 channels (12)(13)(14). It is possible that the native currents resulted from the presence of other calcium channel isoforms (i.e.…”

“…The electrophysiological properties of Ca V 1.4 channels are supportive of its physiological role as glutamate release at the photoreceptor synapse occurs in a sustained and graded manner. However, the electrophysiological properties characterized using heterologously expressed Ca V 1.4 channels differed from the properties of the native Ca 2ϩ currents measured at the rod photoreceptors and bipolar cells (12)(13)(14). The heterologously expressed channels activated at membrane potentials that were ϳ30 mV more positive compared with the rod Ca 2ϩ currents.…”

TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals

“…This includes Ca 2ϩ buffering systems like Ca 2ϩ sequestration and release from internal stores Suryanarayanan and Slaughter, 2006), Ca 2ϩ extrusion by plasma membrane Ca 2ϩ ATPases (PMCAs) (Morgans et al, 1998) and modulation of Ca 2ϩ -dependant inactivation (Zühlke et al, 1999;Singh et al, 2006). Furthermore, additional membrane conductances like large Ca 2ϩ -activated chloride currents have been measured in photoreceptors (Bader et al, 1982;Maricq and Korenbrot, 1988;Cia et al, 2005). The interaction between Ca 2ϩ currents and Ca 2ϩ -activated chloride currents is believed to regulate synaptic output by local feedback mechanisms (Thoreson et al, 2003;Thoreson and Bryson, 2004); however, the molecular identity of Ca 2ϩ -activated chloride channels (CaCCs) in photoreceptors is currently unknown.…”