Role of extracellular Ca2+ in gating of CaV1.2 channels |
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Authors: | Olga Babich Dmytro Isaev Roman Shirokov |
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Institution: | Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA |
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Abstract: | We examined changes in ionic and gating currents in CaV1.2 channels when extracellular Ca2+ was reduced from 10 m m to 0.1 μ m . Saturating gating currents decreased by two-thirds ( K D≈ 40 μ m ) and ionic currents increased 5-fold ( K D≈ 0.5 μ m ) due to increasing Na+ conductance. A biphasic time dependence for the activation of ionic currents was observed at low Ca2+], which appeared to reflect the rapid activation of channels that were not blocked by Ca2+ and a slower reversal of Ca2+ blockade of the remaining channels. Removal of Ca2+ following inactivation of Ca2+ currents showed that Na+ currents were not affected by Ca2+-dependent inactivation. Ca2+-dependent inactivation also induced a negative shift of the reversal potential for ionic currents suggesting that inactivation alters channel selectivity. Our findings suggest that activation of Ca2+ conductance and Ca2+-dependent inactivation depend on extracellular Ca2+ and are linked to changes in selectivity. |
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