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1 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
We examined changes in ionic and gating currents in CaV1.2 channels when extracellular Ca2+ was reduced from 10 mM to 0.1 µM. Saturating gating currents decreased by two-thirds (KD
40 µM) and ionic currents increased 5-fold (KD
0.5 µM) 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.
(Received 11 March 2005;
accepted after revision 15 April 2005;
first published online 21 April 2005)
Corresponding author R. Shirokov: Department of Pharmacology and Physiology, UMDNJ, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. Email: roman.shirokov{at}umdnj.edu
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