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Calcium‐activated BK Ca channels govern dynamic membrane depolarizations of horizontal cells in rodent retina
Author(s) -
Sun Xiaoping,
Hirano Arlene A.,
Brecha Nicholas C.,
Barnes Steven
Publication year - 2017
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp274132
Subject(s) - bk channel , iberiotoxin , depolarization , biophysics , chemistry , membrane potential , calcium activated potassium channel , hyperpolarization (physics) , t type calcium channel , divalent , potassium channel , calcium , voltage dependent calcium channel , neuroscience , biology , stereochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
Key points Large conductance, Ca 2+ ‐activated K + (BK Ca ) channels play important roles in mammalian retinal neurons, including photoreceptors, bipolar cells, amacrine cells and ganglion cells, but they have not been identified in horizontal cells. BK Ca channel blockers paxilline and iberiotoxin, as well as Ca 2+ free solutions and divalent cation Ca v channel blockers, eliminate the outwardly rectifying current, while NS1619 enhances it. In symmetrical 150 m m K + , single channels had a conductance close to 250 pS, within the range of all known BK Ca channels. In current clamped horizontal cells, BK Ca channels subdue depolarizing membrane potential excursions, reduce the average resting potential and decrease oscillations. The results show that BK Ca channel activation puts a ceiling on horizontal cell depolarization and regulates the temporal responsivity of the cells.Abstract Large conductance, calcium‐activated potassium (BK Ca ) channels have numerous roles in neurons including the regulation of membrane excitability, intracellular [Ca 2+ ] regulation, and neurotransmitter release. In the retina, they have been identified in photoreceptors, bipolar cells, amacrine cells and ganglion cells, but have not been conclusively identified in mammalian horizontal cells. We found that outward current recorded between −30 and +60 mV is carried primarily in BK Ca channels in isolated horizontal cells of rats and mice. Whole‐cell outward currents were maximal at +50 mV and declined at membrane potentials positive to this value. This current was eliminated by the selective BK Ca channel blocker paxilline (100 n m ), iberiotoxin (10 μ m ), Ca 2+ free solutions and divalent cation Ca v channel blockers. It was activated by the BK Ca channel activator NS1619 (30 μ m ). Single channel recordings revealed the conductance of the channels to be 244 ± 11 pS ( n = 17; symmetrical 150 m m K + ) with open probability being both voltage‐ and Ca 2+ ‐dependent. The channels showed fast activation kinetics in response to Ca 2+ influx and inactivation gating that could be modified by intracellular protease treatment, which suggests β subunit involvement. Under current clamp, block of BK Ca current increased depolarizing membrane potential excursions, raising the average resting potential and producing oscillations. BK Ca current activation with NS1619 inhibited oscillations and hyperpolarized the resting potential. These effects underscore the functional role of BK Ca current in limiting depolarization of the horizontal cell membrane potential and suggest actions of these channels in regulating the temporal responsivity of the cells.