Whole cell and single-channel properties of a unique voltage-activated sustained calcium current identified in teleost retinal horizontal cells

Abstract

1. A voltage-activated, sustained calcium current in white bass retinal cone horizontal cells was characterized on the basis of electrophysiological and pharmacological criteria. Studies were performed with the use of a combination of whole cell and single-channel analysis of outside-out excised patches from isolated, cultured retinal horizontal cells. 2. We found that the white bass sustained calcium channel represents a unique type of calcium channel. On the basis of our analysis, it does not fall into any current classification scheme. The horizontal cell channel shares some biophysical and pharmacological properties with the typical high-voltage-activated L-type channel, but it also has features in common with the P-type channel. 3. The biophysical characteristics of the channel were most typical of an L-type channel. It activated above -30 mV membrane potential and only very slowly inactivated. It had a single-channel conductance of 25 pS. 4. Like the typical L-type current, the horizontal cell current was sensitive to the dihydropyridine agonist Bay K 8644. It prolonged the channel open time, which resulted in a large increase in macroscopic current flow into the cell. However, unlike the typical L current, dihydropyridine antagonists (nifedipine, nimodipine, etc.) as well as the specific L-channel inhibitor diltiazem were only moderately effective at best. 5. In a previous study, we found the current was antagonized by a factor found in funnel-web spider toxin. Here we show that the current is completely blocked by low doses of omega-agatoxin IVA. These are characteristics of the P-type calcium channel. But unlike the P current, the horizontal cell current is relatively insensitive to low or high doses of omega-conotoxin MVIIC. 6. The overall combination of calcium channel characteristics sets apart the calcium channel in bass horizontal cells from previously described channels. It appears to be a unique, tissue-specific ion channel, which we have labeled the PL channel.

Calcium-induced calcium release and calcium buffering in retinal horizontal cells

“…The magnitude of the calcium responses decreased for depolarizations beyond 10 mVs. This is very similar in shape to the I-V relationships of the underlying calcium currents (Pfeiffer- Linn & Lasater, 1996). Unlike the calcium responses that increased throughout the duration of the 10-s depolarization, the corresponding calcium currents reached a maximal level within a few milliseconds following depolarization onset (Fig.…”

“…First, through the activation of the glutamate receptor0channel complex, primarily of the AMPA-type, that is permeable to monovalent as well as divalent cations such as calcium (Linn & Christensen, 1992;Okada et al, 1999). In addition, calcium can also flow into the cells by way of voltage-gated calcium channels of the T-and P0L-type, with the P0L-type channels contributing to a constant influx of calcium ions during sustained depolarizations (Sullivan & Lasater, 1992;Pfeiffer-Linn & Lasater, 1996). To counteract the continued inflow of calcium, horizontal cells are endowed with calcium-regulating mechanisms common to other neuronal types.…”

Localization of voltage‐sensitive L‐type calcium channels in the chicken retina

“…Evidence suggests that L‐type calcium channels mediate the calcium influx required for the sustained release of neuromodulators and neurotransmitters at many synapses in the retina. In support of this, slowly inactivating L‐type calcium currents have been measured in many retinal cells, including photoreceptors, 1 horizontal cells, 2,3 bipolar cells 4–7 and Müller cells 8 . In addition, dihydropyridine antagonists, which block L‐type calcium channel function, block the release of glutamate in Xenopus photoreceptors, 9 and in chickens, the release of melatonin from photoreceptors is also regulated by an L‐type calcium current 10 …”

Diltiazem-induced Neuroprotection in Glutamate Excitotoxicity and Ischemic Insult of Retinal Neurons

“…Ca 2+ permeability of AMPA receptors was reported in bipolar and horizontal cells [12], and amacrines cells [13,14]. By contrast to other areas of the CNS where neurons mainly express N-type and P/Q-type voltage-gated Ca 2+ channels [15], retinal neurons generate Ca 2+ fluxes through L-type channels [16][17][18]. These channels possess the higher Ca 2+ conductance and the less pronounced desensitisation, properties particularly adapted for retinal graded potential neurotransmission.…”