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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Hypothermia increases the gain of excitation-contraction coupling in guinea pig ventricular myocytes

¹Department of Pharmacology and Division of Geriatric Medicine, Dalhousie University, Halifax, NS, Canada B3H 1X5; ²Jim and Pat Calhoun Cardiology Center, University of Connecticut Health Center, Farmington, Connecticut

Submitted 2 June 2008 ; accepted in final form 9 July 2008

Components of excitation-contraction (EC)-coupling were compared at 37°C and 22°C to determine whether hypothermia altered the gain of EC coupling in guinea pig ventricular myocytes. Ca²⁺ 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°C), Ca²⁺ transients (157 ± 33 vs. 35 ± 5 nM at 37°C), and diastolic Ca²⁺ (100 ± 9 vs. 60 ± 6 nM at 37°C) in field-stimulated myocytes (2 Hz). In experiments with high-resistance microelectrodes, the increase in contractions and Ca²⁺ 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 Ca²⁺ transients. Hypothermia increased sarcoplasmic reticulum (SR) Ca²⁺ stores (83 ± 17 at 37°C to 212 ± 50 nM, assessed with caffeine) and increased fractional SR Ca²⁺ release twofold. In contrast, peak Ca²⁺ current was much smaller at 22°C than at 37°C (1.3 ± 0.4 and 3.5 ± 0.7 pA/pF, respectively). In cells dialyzed with sodium-free pipette solutions to inhibit Ca²⁺ influx via reverse-mode Na⁺/Ca²⁺ exchange, hypothermia still increased contractions, Ca²⁺ transients, SR stores, and fractional release but decreased the amplitude of Ca²⁺ current. The rate of SR Ca²⁺ release per unit Ca²⁺ 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.

positive inotropy; calcium transient; contraction; calcium current; sarcoplasmic reticulum calcium stores