The dihydropyridine-sensitive calcium channel subtype in cone photoreceptors.

Abstract

ABSTgACT High-voltage activated Ca channels in tiger salamander cone photoreceptors were studied with nystatin-permeabilized patch recordings in 3 mM Ca 2+ and 10 mMBa 2+. The majority of Ca channel current was dihydropyridine sensitive, suggesting a preponderance of L-type Ca channels. However, voltage-dependent, incomplete block (maximum 60%) by nifedipine (0.1-100 IzM) was evident in recordings of cones in tissue slice. In isolated cones, where the block was more potent, nifedipine (0.1-10 ~M) or nisoldipine (0.5-5 ~M) still failed to eliminate completely the Ca channel current. Nisoldipine was equally effective in blocking Ca channel current elicited in the presence of 10 mM Ba z+ (76% block) or 3 mM Ca 2+ (88% block). 15% of the Ba z+ current was reversibly blocked by 0~-conotoxin GVIA (1 p.M). After enhancement with 1 I*M Bay K 8644, t0-conotoxin GVIA blocked a greater proportion (22%) of Ba 2+ current than in control. After achieving partial block of the Ba 2+ current with nifedipine, concomitant application of t0-conotoxin GVIA produced no further block. The P-type Ca channel blocker, ~0-agatoxin IVA (200 nM), had variable and insignificant effects. The current persisting in the presence of these blockers could be eliminated with Cd 2+ (100 ~M). These results indicate that photoreceptors express an L-type Ca channel having a distinguishing pharmacological profile similar to the ~m Ca channel subtype. The presence of additional Ca channel subtypes, resistant to the widely used L-, N-, and P-type Ca channel blockers, cannot, however, be ruled out.

Thenob2mouse, a null mutation inCacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses

“…It is possible that another VDCC α 1 subunit may be expressed and support at least partial synapse formation with the cone pedicle. This idea is supported by reports of α 1D expression in cone terminals (Wilkinson & Barnes, 1996;Taylor & Morgans, 1998;Morgans, 1999, Morgans et al, 2001 and is consistent with the greater ERG b-wave deficit in mice lacking the VDCC β 2 subunit (Ball et al, 2002), the only VDCC β subunit known to be expressed in the OPL (Ball et al, 2004).…”

T-type channels-secretion coupling: evidence for a fast low-threshold exocytosis

“…Evidence for a contribution of R-type channels on glutamate release is reported at the calyx of Held [71], and R-type channels are shown to replace P/Q-type channels at the mouse neuromuscular junction in KO mice lacking P/Q-type channels [67]. Ltype channels are shown to control glutamate release in rod photoreceptor terminals [69] and to colocalize at the hot spots of bipolar cell terminals [5]. L-type channels are expressed also in AII amacrine cells and localized at the distal dendrites where synaptic transmission takes place [27].…”

Synaptic transmission at retinal ribbon synapses

“…The 10 genes are grouped into three families (1, 2, 3) with multiple subtypes. In this review, we concentrate upon the L-type Ca 2+ channels responsible for exocytosis from photoreceptor and bipolar cells (Corey et al, 1984;Wilkinson and Barnes, 1996;Thoreson et al, 1997;Schmitz and Witkovsky, 1997;Heidelberger and Matthews, 1992;; but see also Pan et al, 2001). Although formerly designated variously as L-type, high voltageactivated or dihydropyridine-sensitive, in the latest naming scheme, all are part of the Ca v 1 subfamily (Catterall et al, 2003).…”

“…Light moves the membrane potential in a graded fashion to more hyperpolarized levels, creating an operating range for the photoreceptors of −40 to −65 mV. The Ca 2+ channel(s) of rods and cones must smoothly regulate Ca 2+ entry in this voltage range and it has long been a puzzle to investigators that −40 mV is just at the foot of the I Ca activation function measured in rods and cones of lower vertebrates (Corey et al, 1984;Lasater and Witkovsky, 1991;Wilkinson and Barnes, 1996). In contrast, three studies of I Ca in mammalian cones revealed a relatively large current at −40 mV (Yagi and MacLeish, 1994;Taylor and Morgans, 1998;De Vries and Schwartz, 1999).…”