Gender influences coronary L-type Ca2+ current and adaptation to exercise training in miniature swine

Endurance exercise training increases smooth muscle L-type Ca2+ current density in both resistance and proximal coronary arteries of female miniature swine. The purpose of the present study was to determine 1) whether gender differences exist in coronary smooth muscle (CSM) L-type Ca2+ current; density and 2) whether endurance training in males would demonstrate a similar adaptive response as females. Proximal, conduit (similar to1.0 mm), and resistance [similar to 200 mum (internal diameter)] coronary arteries were obtained from sedentary and treadmill-trained swine of both sexes. CSM were isolated by enzymatic digestion (collagenase plus elastase), and voltage-gated Ca2+-channel current (I-Ca) was determined by using whole cell voltage clamp during superfusion with 75 mM tetraethylammonium chloride and 10 mM BaCl2. Current-voltage relationships were obtained at test potentials from -60 to 70 mV from a holding potential of -80 mV, and I-Ca was normalized to cell capacitance (pA/pF). Endurance treadmill training resulted in similar increases in heart weight-to-body weight ratio, endurance time, and skeletal muscle citrate synthase activity in male and female swine. I-Ca. density was significantly greater in males compared with females in both conduit (- 7.57 +/- 0.58 vs. - 4.14 +/- 0.47 pA/pF) and resistance arteries (-11.25 +/- 0.74 vs. -6.49 +/- 0.87 pA/pF, respectively). In addition, voltage-dependent activation of I-Ca in resistance arteries was shifted to more negative membrane potentials in males. Exercise training significantly increased I-Ca density in both conduit and resistance arteries in females (-7.01 +/- 0.47 and -9.73 +/- 1.13 pA/pF, respectively) but had no effect in males (-8.61 +/- 0.50 and -12.04 +/- 1.07 pA/pF, respectively). Thus gender plays a significant role in determining both the magnitude and voltage dependence of I-Ca in CSM and the adaptive response of I-Ca to endurance training.