Biphasic effects of hyposmotic challenge on excitation-contraction coupling in rat ventricular myocytes.
The effects of short (1 min) and long (7-10 min) exposure to hyposmotic solution on excitation-contraction coupling in rat ventricular myocytes were studied. After short exposure, the action potential duration at 90% repolarization (APD(90)), the intracellular Ca(2+) concentration ([Ca(2+)](i)) transient amplitude, and contraction increased, whereas the L-type Ca(2+) current (I(Ca, L)) amplitude decreased. Fractional sarcoplasmic reticulum (SR) Ca(2+) release increased but SR Ca(2+) load did not. After a long exposure, I(Ca,L), APD(90), [Ca(2+)](i) transient amplitude, and contraction decreased. The abbreviation of APD(90) was partially reversed by 50 microM DIDS, which is consistent with the participation of Cl(-) current activated by swelling. After 10-min exposure to hyposmotic solution in cells labeled with di-8-aminonaphthylethenylpyridinium, t-tubule patterning remained intact, suggesting the loss of de-t-tubulation was not responsible for the fall in I(Ca,L). After long exposure, Ca(2+) load of the SR was not increased, and swelling had no effect on the site-specific phosphorylation of phospholamban, but fractional SR Ca(2+) release was depressed. The initial positive inotropic response to hyposmotic challenge may be accounted for by enhanced coupling between Ca(2+) entry and release. The negative inotropic effect of prolonged exposure can be accounted for by shortening of the action potential duration and a fall in the I(Ca,L) amplitude.
Brette
F
F
School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, United Kingdom.
Calaghan
S C
SC
Lappin
S
S
White
E
E
Colyer
J
J
Le Guennec
J Y
JY
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D008297:Male; D008870:Microtubules / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009995:Osmosis; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology; D012996:Solutions; D013395:Sucrose / Q000494:pharmacology; D016276:Ventricular Function
D020746:Calcium Channels, L-Type; D012996:Solutions; D012965:Sodium Chloride; D013395:Sucrose; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium