FPL-64176 modifies pore properties of L-type Ca(2+) channels.
In addition to its known effects on Ca(2+) and Ba(2+) currents, the L-type Ca(2+) channel agonist FPL-64176 was found to affect channel function in isolated rat ventricular myocytes in the absence of Ca(2+), with other ions as current carriers through the channel. FPL-64176 induced Cd(2+) current through the L-type Ca(2+) channel, suggesting that certain selectivity properties had changed, perhaps indicative of a small change in pore structure. FPL-64176 slightly but significantly decreased the effectiveness of Co(2+) as a blocker of the channel. FPL-64176 also increased conductance through single L-type Ca(2+) channels recorded in the cell-attached configuration, from 71.9 +/- 11.6 to 94.1 +/- 8.3 pS, with Na(+) carrying the current at pH 9.0. At present it is uncertain whether FPL-64176 produces small alterations of a sole open state of the channel or whether it increases the prevalence of a second, higher conductance open state. These changes, particularly the conversion of Cd(2+) from a pure blocker to a permeant ion, may be of eventual help in discriminating among different models for Ca(2+) channel selectivity.
Fan
J
J
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555-0641, USA.
Yuan
Y
Y
Palade
P
P
D000818:Animals; D002104:Cadmium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D003035:Cobalt / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004553:Electric Conductivity; D006352:Heart Ventricles; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D011758:Pyrroles; D002104:Cadmium; C071658:FPL 64176; D003035:Cobalt