Role of extracellular Ca2+ in gating of CaV1.2 channels.
We examined changes in ionic and gating currents in Ca(V)1.2 channels when extracellular Ca(2+) was reduced from 10 mm to 0.1 microm. Saturating gating currents decreased by two-thirds (K(D) approximately 40 microm) and ionic currents increased 5-fold (K(D) approximately 0.5 microm) due to increasing Na(+) conductance. A biphasic time dependence for the activation of ionic currents was observed at low [Ca(2+)], which appeared to reflect the rapid activation of channels that were not blocked by Ca(2+) and a slower reversal of Ca(2+) blockade of the remaining channels. Removal of Ca(2+) following inactivation of Ca(2+) currents showed that Na(+) currents were not affected by Ca(2+)-dependent inactivation. Ca(2+)-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 Ca(2+) conductance and Ca(2+)-dependent inactivation depend on extracellular Ca(2+) and are linked to changes in selectivity.
Babich
Olga
O
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.
Isaev
Dmytro
D
Shirokov
Roman
R
D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002460:Cell Line; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D008564:Membrane Potentials / Q000502:physiology
D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D002118:Calcium