Electrophysiological response of rat atrial myocytes to acidosis.
The effect of acidosis on the electrical activity of isolated rat atrial myocytes was investigated using the patch-clamp technique. Reducing the pH of the bathing solution from 7.4 to 6.5 shortened the action potential. Acidosis had no significant effect on transient outward or inward rectifier currents but increased steady-state outward current. This increase was still present, although reduced, when intracellular Ca(2+) was buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA); BAPTA also inhibited acidosis-induced shortening of the action potential. Ni(2+) (5 mM) had no significant effect on the acidosis-induced shortening of the action potential. Acidosis also increased inward current at -80 mV and depolarized the resting membrane potential. Acidosis activated an inwardly rectifying Cl(-) current that was blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which also inhibited the acidosis-induced depolarization of the resting membrane potential. It is concluded that an acidosis-induced increase in steady-state outward K(+) current underlies the shortening of the action potential and that an acidosis-induced increase in inwardly rectifying Cl(-) current underlies the depolarization of the resting membrane potential during acidosis.
School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, United Kingdom.
Kimiaki
K
Komukai
Fabien
F
Brette
Clive H
CH
Orchard
D000138:Acidosis / Q000473:pathology / Q000503:physiopathology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016275:Atrial Function; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004594:Electrophysiology; D006706:Homeostasis; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D009206:Myocardium / Q000473:pathology; D009532:Nickel / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002021:Buffers; D002614:Chelating Agents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D004533:Egtazic Acid; D009532:Nickel; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium