Hypothermia increases the gain of excitation-contraction coupling in guinea pig ventricular myocytes.
Components of excitation-contraction (EC)-coupling were compared at 37 degrees C and 22 degrees C to determine whether hypothermia altered the gain of EC coupling in guinea pig ventricular myocytes. Ca(2+) concentration (fura-2) and cell shortening (edge detector) were measured simultaneously. Hypothermia increased fractional shortening (8.3+/-1.7 vs. 2.6+/-0.3% at 37 degrees C), Ca(2+) transients (157+/-33 vs. 35+/-5 nM at 37 degrees C), and diastolic Ca(2+) (100+/-9 vs. 60+/-6 nM at 37 degrees C) in field-stimulated myocytes (2 Hz). In experiments with high-resistance microelectrodes, the increase in contractions and Ca(2+) transients was accompanied by a twofold increase in action potential duration (APD). When voltage-clamp steps eliminated changes in APD, cooling still increased contractions and Ca(2+) transients. Hypothermia increased sarcoplasmic reticulum (SR) Ca(2+) stores (83+/-17 at 37 degrees C to 212+/-50 nM, assessed with caffeine) and increased fractional SR Ca(2+) release twofold. In contrast, peak Ca(2+) current was much smaller at 22 degrees C than at 37 degrees C (1.3+/-0.4 and 3.5+/-0.7 pA/pF, respectively). In cells dialyzed with sodium-free pipette solutions to inhibit Ca(2+) influx via reverse-mode Na(+)/Ca(2+) exchange, hypothermia still increased contractions, Ca(2+) transients, SR stores, and fractional release but decreased the amplitude of Ca(2+) current. The rate of SR Ca(2+) release per unit Ca(2+) current, a measure of EC-coupling gain, was increased sixfold by hypothermia. This increase in gain occurred regardless of whether cells were dialyzed with sodium-free solutions. Thus an increase in EC-coupling gain contributes importantly to positive inotropic effects of hypothermia in the heart.
Shutt
Robin H
RH
Jim and Pat Calhoun Cardiology Center, University of Connecticut Health Center, Farmington, Connecticut, USA.
Howlett
Susan E
SE
D000200:Action Potentials; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D048429:Cell Size; D003080:Cold Temperature; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000378:metabolism; D007035:Hypothermia / Q000378:metabolism* / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013997:Time Factors
D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D012964:Sodium