RT Journal Article SR Electronic T1 Single-Channel Pharmacology of Mibefradil in Human Native T-Type and Recombinant Cav3.2 Calcium Channels JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 682 OP 694 DO 10.1124/mol.61.3.682 VO 61 IS 3 A1 Guido Michels A1 Jan Matthes A1 Renate Handrock A1 Ute Kuchinke A1 Ferdi Groner A1 Leanne L. Cribbs A1 Alexey Pereverzev A1 Toni Schneider A1 Edward Perez-Reyes A1 Stefan Herzig YR 2002 UL http://molpharm.aspetjournals.org/content/61/3/682.abstract AB To study the molecular pharmacology of low-voltage–activated calcium channels in biophysical detail, human medullary thyroid carcinoma (hMTC) cells were investigated using the single-channel technique. These cells had been reported to express T-type whole-cell currents and a Cav3.2 (or α1H) channel subunit. We observed two types of single-channel activity that were easily distinguished based on single-channel conductance, voltage dependence of activation, time course of inactivation, rapid gating kinetics, and the response to the calcium agonist (S)-Bay K 8644. Type II channels had biophysical properties (activation, inactivation, conductance) typical for high-voltage–activated calcium channels. They were markedly stimulated by 1 μM (S)-Bay K 8644, allowing to identify them as L-type channels. The channel termed type I is a low-voltage–activated, small-conductance (7.2 pS) channel that inactivates rapidly and is not modulated by (S)-Bay K 8644. Type I channels are therefore classified as T-type channels. They were strongly inhibited by 10 μM mibefradil. Mibefradil block was caused by changes in two gating parameters: a pronounced reduction in fraction of active sweeps and a slight shortening of the open-state duration. Single recombinant low-voltage–activated T-type calcium channels were studied in comparison, using human embryonic kidney 293 cells overexpressing the pore-forming Cav3.2 subunit. Along all criteria examined (mechanisms of block, extent of block), recombinant Cav3.2 interact with mibefradil in the same way as their native counterparts expressed in hMTC cells. In conclusion, the pharmacologic phenotype of these native human T-type channels—as probed by mibefradil—is similar to recombinant human Cav3.2.