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Am J Physiol Cell Physiol 280: C565-C572, 2001;
0363-6143/01 $5.00
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Vol. 280, Issue 3, C565-C572, March 2001

FPL-64176 modifies pore properties of L-type Ca2+ channels

Jing-Song Fan1, Yuhui Yuan1, and Philip Palade1,2

Departments of 1 Physiology and Biophysics and 2 Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555-0641

In addition to its known effects on Ca2+ and Ba2+ currents, the L-type Ca2+ channel agonist FPL-64176 was found to affect channel function in isolated rat ventricular myocytes in the absence of Ca2+, with other ions as current carriers through the channel. FPL-64176 induced Cd2+ current through the L-type Ca2+ 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 Co2+ as a blocker of the channel. FPL-64176 also increased conductance through single L-type Ca2+ 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 Cd2+ from a pure blocker to a permeant ion, may be of eventual help in discriminating among different models for Ca2+ channel selectivity.

cardiac myocytes; Cd2+; Co2+; conductance; selectivity


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