Ca(2+)-activated Cl(-) current in rabbit sinoatrial node cells.
The Ca(2+)-activated Cl(-) current (I(Cl(Ca))) has been identified in atrial, Purkinje and ventricular cells, where it plays a substantial role in phase-1 repolarization and delayed after-depolarizations. In sinoatrial (SA) node cells, however, the presence and functional role of I(Cl(Ca)) is unknown. In the present study we address this issue using perforated patch-clamp methodology and computer simulations. Single SA node cells were enzymatically isolated from rabbit hearts. I(Cl(Ca)) was measured, using the perforated patch-clamp technique, as the current sensitive to the anion blocker 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS). Voltage clamp experiments demonstrate the presence of I(Cl(Ca)) in one third of the spontaneously active SA node cells. The current was transient outward with a bell-shaped current-voltage relationship. Adrenoceptor stimulation with 1 microM noradrenaline doubled the I(Cl(Ca)) density. Action potential clamp measurements demonstrate that I(Cl(Ca)) is activate late during the action potential upstroke. Current clamp experiments show, both in the absence and presence of 1 microM noradrenaline, that blockade of I(Cl(Ca)) increases the action potential overshoot and duration, measured at 20 % repolarization. However, intrinsic interbeat interval, upstroke velocity, diastolic depolarization rate and the action potential duration measured at 50 and 90 % repolarization were not affected. Our experimental data are supported by computer simulations, which additionally demonstrate that I(Cl(Ca)) has a limited role in pacemaker synchronization or action potential conduction. In conclusion, I(Cl(Ca)) is present in one third of SA node cells and is activated during the pacemaker cycle. However, I(Cl(Ca)) does not modulate intrinsic interbeat interval, pacemaker synchronization or action potential conduction.
Verkerk
Arie O
AO
Academic Medical Center, University of Amsterdam, Task Force Heart Failure and Aging, Department of Physiology, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. A.O.Verkerk@amc.uva.nl
Wilders
Ronald
R
Zegers
Jan G
JG
van Borren
Marcel M G J
MM
Ravesloot
Jan H
JH
Verheijck
E Etienne
EE
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; D001683:Biological Clocks / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D003198:Computer Simulation; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000592:standards; D011817:Rabbits; D015203:Reproducibility of Results; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D002712:Chlorides; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium; D009638:Norepinephrine