Role of Ca(2+)-activated Cl(-) current in ventricular action potentials of sheep during adrenoceptor stimulation.
Adrenoceptor stimulation enhances repolarising and depolarising membrane currents to different extents in cardiac myocytes. We investigated the opposing effects of the repolarising Ca(2+)-activated Cl(-) current (I(Cl(Ca))) and depolarising L-type Ca(2+) current (I(Ca,L)) on the action potential configuration of sheep ventricular myocytes stimulated with noradrenaline. Whole-cell current-clamp recordings revealed that noradrenaline accelerated and prolonged phase-1 repolarisation. We define the minimal potential at the end of phase-1 repolarisation as "notch level". Noradrenaline (1 microM) caused the notch level to fall from 14 +/- 2.6 to 7.8 +/- 2.8 mV (n = 24), but left action potential duration, resting membrane potential or action potential amplitude unaffected. Whole-cell voltage-clamp recordings showed that 1 microM noradrenaline increased both I(Ca,L) and I(Cl(Ca)), but it had no significant effect on the principal K(+) currents. Blockage of I(Cl(Ca)) by 0.5 mM 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) in both the absence and the presence of noradrenaline abolished phase-1 repolarisation. In the presence of noradrenaline, DIDS caused elevation of the plateau phase amplitude and an increase in the action potential duration. In conclusion, elevation of the plateau phase amplitude and action potential prolongation associated with an increased I(Ca,L) upon adrenoceptor stimulation is prevented by an increased I(Cl(Ca)) in sheep ventricular myocytes. Experimental Physiology (2001) 86.2, 151-159.
Verkerk
A O
AO
Department of Physiology, Academic Medical Center, University of Amsterdam, The Netherlands. A.O.Verkerk@amc.uva.nl
Schumacher
C A
CA
van Ginneken
A C
AC
Veldkamp
M W
MW
Ravesloot
J H
JH
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002412:Cations / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D009638:Norepinephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011941:Receptors, Adrenergic / Q000502:physiology*; D012756:Sheep; D016276:Ventricular Function
D000316:Adrenergic alpha-Agonists; D020746:Calcium Channels, L-Type; D002412:Cations; D018118:Chloride Channels; D015221:Potassium Channels; D011941:Receptors, Adrenergic; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium; D009638:Norepinephrine