Abstract
Calcium currents of the cardiac plasma membrane were first found as slow inward currents (Is) in multi-cellular preparations using the sucrose-gap voltage clamp method. I published the properties of Is and novel Mn current in guinea pig papillary muscle from W Trautwein's laboratory in Heidelberg (1970). Whole-cell Mn current flowed through the L-type Ca channel with a density of 8% of Ca current. Reevaluation of the trigger action versus the membrane potential relationship in Heidelberg suggests that Is is responsible for the trigger action, as expected from CICR. Is was inhibited by acetylcholine and gentamicin. A single Ca channel study demonstrated the following : 1) BAY K 8644 greatly prolonged the open time of the Ca channel, 2) nitrendipine (NIT) decreased the channel availability (Ps), 3) isoproterenol (ISO) prolonged the non-blank run (S-state) and shortened blank run (F state) to increase Ps, 4) adenosine decreased Ps in the presence of ISO, and 5) Ps was increased by 5-HT in human atrial myocytes. A whole-cell clamp study demonstrated the following : 1) the independent modulation of L-type channel currents by ISO and NIT, 2) currents by extrinsic expression of α1E subunit to cultured adult rabbit ventricular myocytes, 3) L-type Ca channels in hepatic satellite cells, and 4) epiandrosteroneinduced blockade of L-type Ca channel current. I consider our most valuable work to be the single channel analysis of the mechanism of sympathetic regulation of cardiac L-type Ca channels.
