Effects of acidosis on Na+/Ca2+ exchange and consequences for relaxation in guinea pig cardiac myocytes.
We investigated the effect of intracellular acidosis (imposed by NH4Cl prepulses) on the relaxation and decline in intracellular Ca2+ (using indo 1 fluorescence) of isolated cardiac myocytes from the guinea pig. Acidosis produced a decrease in contraction and a prolongation of the fluorescence transient. The rate of decline in fluorescence after a rapid-cooling contracture was slower in acidosis compared with control. The decline in fluorescence after a rapid-cooling contracture in the presence of 10 mM caffeine was greatly slowed during acidosis, suggesting that Na+/Ca2+ exchange is affected. We recorded indo 1 fluorescence and the transient inward current in voltage-clamped cells on rapid application of 10 mM caffeine under control conditions and in acidosis. The amplitude of the transient increase in fluorescence was reduced in acidosis and the decline in fluorescence slowed. The current showed no difference in amplitude in acidosis, but the time to 50% recovery was increased by 57%. When amiloride or ethylisopropylamiloride was present, no differences in the current were found between control and acidosis, and the times to 50% recovery were similar. We conclude that intracellular acidosis slows Ca2+ efflux via Na+/Ca2+ exchange because of an increase in intracellular Na+ due to enhanced Na+/H+ exchange activity.
Terracciano
C M
CM
Department of Cardiac Medicine, University of London, United Kingdom.
MacLeod
K T
KT
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003080:Cold Temperature; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007211:Indoles; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D013997:Time Factors
D002352:Carrier Proteins; D007211:Indoles; D019831:Sodium-Calcium Exchanger; D000643:Ammonium Chloride; D002110:Caffeine; C048960:indo-1; D002118:Calcium