RT Journal Article
SR Electronic
T1 Mibefradil Inhibition of T-Type Calcium Channels in Cerebellar Purkinje Neurons
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1080
OP 1087
DO 10.1124/mol.54.6.1080
VO 54
IS 6
A1 Stefan I. McDonough
A1 Bruce P. Bean
YR 1998
UL http://molpharm.aspetjournals.org/content/54/6/1080.abstract
AB The antihypertensive agent mibefradil completely and reversibly inhibited T-type calcium channels in freshly isolated rat cerebellar Purkinje neurons. The potency of mibefradil was increased at less hyperpolarized holding potentials, and the apparent affinity was correlated with the degree of channel inactivation. At 35°, the apparent dissociation constant K app was 1 μm at a holding voltage of −110 mV (corresponding to noninactivated channels) and 83 nm at a holding voltage of −70 mV (corresponding to 65% inactivation). The increased affinity was attributable mainly to a decreased off-rate. Mibefradil also inhibited P-type calcium channels in Purkinje neurons, but inhibition was much less potent. At a holding potential of −70 mV, theK app for mibefradil inhibition of P-type channels was ∼200-fold higher than that for inhibition of T-type channels. Mibefradil should be a useful compound for distinguishing T-type channels from high voltage-activated calcium channels in neurons studied in vitro.