beta-Adrenergic modulation of prepulse facilitation of L-type calcium channels in rabbit ventricular myocytes.
It is reported that strong depolarization augments cardiac L-type Ca currents by inducing the special gating mode with long-lasting openings (mode 2) (Pietrobon and Hess Nature 346:651-655, 1990). However, a prepulse to +90 mV did not obviously facilitate the current at 0 mV in rabbit ventricular myocytes as measured in the whole-cell configuration of the patch-clamp method in the presence of 2 mM BaCl(2) in the external solution. In the presence of isoproterenol (1 microM), the inactivation during the prepulse was attenuated, and the prepulse evoked facilitation. However, the current at 0 mV whose amplitude was normalized to the extent of the inactivation at +90 mV still exhibited greater facilitation in the presence than in the absence of isoproterenol. In the cell-attached configuration with 110 mM BaCl(2) in pipettes, repolarization from +110 to +20 mV yielded mainly blank sweeps (mode 0) and only occasionally mode 2, leading to no facilitation of the average current. Isoproterenol augmented the prepulse-induced increase in mode 2, reciprocally inhibited that in mode 0, and increased the fraction of mode 2 in non-blank sweeps after the prepulse. Therefore, beta-adrenergic stimulation favors mode 2 rather than mode 0 at strongly depolarized potentials, thereby promoting the prepulse facilitation and attenuating the inactivation of cardiac L-type Ca currents.
Yamada
Mitsuhiko
M
Department of the Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. yamadacp@ri.ncvc.go.jp
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004594:Electrophysiology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol