Slow inactivation of cardiac L-type Ca2+ channel induced by cold acclimation of guinea pig

Departments of Physiology and of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Sakyo ku, Kyoto 606, Japan Whole cell L-type Ca 2+ current was recorded in ventricular myocytes dissociated from guinea pigs that were bred at ambient temperatures ranging between daily averages of 4 and 29°C. The dynamic voltage range of inactivation, as measured using 400-ms conditioning pulses and a holding potential of 40 mV, extended from 50 to 20 mV in myocytes prepared in summer. In winter, the inactivation curve was shifted to more negative potentials than in summer. Double-pulse experiments revealed that the negative shift was due to slow-inactivation kinetics. The negative shift of inactivation could be induced in myocytes prepared from animals that had been kept at 5°C for >3 wk in the summer. The negative shift in Ca 2+ current inactivation could be abolished by adding guanosine 5'- O -(2-thiodiphosphate) (5 mM) to the pipette solution, but not by adding staurosporine (2 µM) or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (100 µM) to the bath. The cold acclimation may introduce the slow inactivation of the cardiac L-type Ca 2+ channel through an unknown pertussis toxin-insensitive G protein. cardiac myocytes; G protein; guanosine 5'- O -(2-thiodiphosphate); cold exposure; inactivation curve; L-type Ca 2+ current