Effects of endothelin-1 on calcium and potassium currents in undiseased human ventricular myocytes.
Endothelins have been reported to exert a wide range of electrophysiological effects in mammalian cardiac cells. These results are controversial and human data are not available. Our aim was to study the effects of endothelin-1 (ET-1, 8 nmol/l) on the L-type calcium current (ICa-L) and various potassium currents (rapid component of the delayed rectifier, IKr; transient outward current, Ito; and the inward rectifier K current, IK1) in isolated human ventricular cardiomyocytes. Cells were obtained from undiseased donor hearts using collagenase digestion via the segment perfusion technique. The whole-cell configuration of the patch-clamp technique was applied to measure ionic currents at 37 degrees C. ET-1 significantly decreased peak ICa-L from 10.2+/-0.6 to 6.8+/-0.8 pA/pF at +5 mV (66.7% of control, P<0.05, n=5). This reduction of peak current was accompanied by a lengthening of inactivation. The voltage dependence of steady-state activation and inactivation was not altered by ET- 1. IKr, measured as tail current amplitudes at 40 mV, decreased from 0.31+/-0.02 to 0.06+/-0.02 pA/pF (20.3% of control, P<0.05, n=4) after exposure to ET-1. ET-1 failed to change the peak amplitude of Ito, measured at +50 mV (9.3+/-4.6 and 9.0+/-4.4 pA/pF before and after ET-1, respectively), or steady-state IK1 amplitude, measured at the end of a 400-ms hyperpolarization to -100 mV (3.6+/-1.4 and 3.7+/-1.4 pA/pF, n=4). The present results indicate that in undiseased human ventricular myocytes ET-1 inhibits both ICa-L and IKr; however, the degree of suppression of the two currents is different.
Magyar
J
J
Department of Physiology, University Medical School of Debrecen, Hungary.
Iost
N
N
Körtvély
A
A
Bányász
T
T
Virág
L
L
Szigligeti
P
P
Varró
A
A
Opincariu
M
M
Szécsi
J
J
Papp
J G
JG
Nánási
P P
PP
D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D004553:Electric Conductivity; D019332:Endothelin-1 / Q000494:pharmacology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D019332:Endothelin-1; D015221:Potassium Channels; D007545:Isoproterenol