Calcium-activated BK Ca channels govern dynamic membrane depolarizations of horizontal cells in rodent retina
Large conductance, Ca -activated K (BK ) 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 channel blockers paxilline and iberiotoxin, as well as Ca free so...
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Veröffentlicht in: | The Journal of physiology 2017-07, Vol.595 (13), p.4449-4465 |
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Zusammenfassung: | Large conductance, Ca
-activated K
(BK
) 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
channel blockers paxilline and iberiotoxin, as well as Ca
free solutions and divalent cation Ca
channel blockers, eliminate the outwardly rectifying current, while NS1619 enhances it. In symmetrical 150 mm K
, single channels had a conductance close to 250 pS, within the range of all known BK
channels. In current clamped horizontal cells, BK
channels subdue depolarizing membrane potential excursions, reduce the average resting potential and decrease oscillations. The results show that BK
channel activation puts a ceiling on horizontal cell depolarization and regulates the temporal responsivity of the cells.
Large conductance, calcium-activated potassium (BK
) channels have numerous roles in neurons including the regulation of membrane excitability, intracellular [Ca
] 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
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
channel blocker paxilline (100 nm), iberiotoxin (10 μm), Ca
free solutions and divalent cation Ca
channel blockers. It was activated by the BK
channel activator NS1619 (30 μm). Single channel recordings revealed the conductance of the channels to be 244 ± 11 pS (n = 17; symmetrical 150 mm K
) with open probability being both voltage- and Ca
-dependent. The channels showed fast activation kinetics in response to Ca
influx and inactivation gating that could be modified by intracellular protease treatment, which suggests β subunit involvement. Under current clamp, block of BK
current increased depolarizing membrane potential excursions, raising the average resting potential and producing oscillations. BK
current activation with NS1619 inhibited oscillations and hyperpolarized the resting potential. These effects underscore the functional role of BK
current in limiting depolarization of the horizontal cell membrane potential and suggest actions of |
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ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/JP274132 |