Exercise training increases L-type calcium current density in coronary smooth muscle

Abstract

Exercise training produces numerous adaptations in the coronary circulation, including an increase in coronary tone, both in conduit and resistance arteries. On the basis of the importance of voltage-gated Ca2+ channels (VGCC) in regulation of vascular tone, we hypothesized that exercise training would increase VGCC current density in coronary smooth muscle. To test this hypothesis, VGCC current was compared in smooth muscle from conduit arteries (>1.0 mm), small arteries (200–250 μm), and large arterioles (75–150 μm) from endurance-trained (Ex) or sedentary miniature swine (Sed). After 16–20 wk of treadmill training, VGCC current was determined using whole cell voltage-clamp techniques. In both Ex and Sed, VGCC current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit arteries. Exercise training increased peak inward currents approximately twofold in smooth muscle from all arterial sizes compared with those from Sed (large arteriole, −12.52 ± 2.05 vs. −5.74 ± 0.99 pA/pF; small artery, −6.20 ± 0.97 vs. −3.18 ± 0.44 pA/pF; and conduit arteries, −4.22 ± 0.30 vs. −2.41 ± 0.55 pA/pF; 10 mM Ba2+ external). Dihydropyridine sensitivity, voltage dependence, and inactivation kinetics identified this Ca2+ current to be L-type current in all arterial sizes from both Sed and Ex. Furthermore, peak VGCC current density was correlated with treadmill endurance in all arterial sizes. We conclude that smooth muscle L-type Ca2+ current density is increased within the coronary arterial bed by endurance exercise training. This increased VGCC density may provide an important mechanistic link between functional and cellular adaptations in the coronary circulation to exercise training.

Exercise Prevents Upregulation of RyRs–BK Ca Coupling in Cerebral Arterial Smooth Muscle Cells From Spontaneously Hypertensive Rats

“…19 One possible mechanism underlying this protection is altered Ca 2+ regulation because of its critical role in the contraction-relaxation cycle of CASMCs, and, most importantly, Ca 2+ homeostasis is affected by chronic endurance exercise. [20][21][22] The close functional relationship between Ca 2+ /current and the activity of K + channels makes alterations in K + channel activity another candidate for the observed effect of exercise-induced cerebral vascular protection.…”

Exercise training attenuates coronary smooth muscle phenotypic modulation and nuclear Ca2+ signaling

“…Adult female Yucatan miniature swine (Charles River; Wilmington, MA) were randomly assigned to either sedentary (SED) or exercise-trained (EX) groups. EX pigs underwent 16 wk of a progressive treadmill exercise-training program used extensively by our laboratories and described previously (7,8,33,41,42). Treadmill performance tests were administered before and after completion of the 16-wk exercise-training program or sedentary confinement as described previously (7,8).…”

“…EX pigs underwent 16 wk of a progressive treadmill exercise-training program used extensively by our laboratories and described previously (7,8,33,41,42). Treadmill performance tests were administered before and after completion of the 16-wk exercise-training program or sedentary confinement as described previously (7,8). Effectiveness of the exercise-training program was determined by comparing running time with exhaustion on treadmill performance tests and skeletal muscle oxidative enzyme activity of EX versus SED animals (see Table 1).…”

“…As previously described in detail (7,9,17,19,20,41,42), proximal right coronary artery segments were opened longitudinally and pinned lumen side up onto a silicone rubber substratum in ϳ2 ml of enzymatic dispersion solution consisting of low-Ca 2ϩ physiological solution plus 294 U/ml collagenase (CLS II, Worthington), 6.5 U/ml elastase (Worthington), 2 mg/ml BSA (fraction V, Sigma), 1 mg/ml soybean trypsin inhibitor (type I-S, Sigma), and 0.4 mg/ml DNase I (type IV, Sigma). Cells were enzymatically dispersed for 45-60 min in a shaking water bath at 37°C.…”

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca2+-sensitive K+ current in miniature swine with LV hypertrophy

“…Training-induced alterations to the coronary vasculature include both increases in smooth muscle cell K ϩ channel activity (6) and reductions in coronary artery sensitivity to ET-1 mediated, in part, by an increase in smooth muscle cell K ϩ channel activation (23). In nonpathological models, exercise has also been shown to impact coronary smooth muscle cell electrophysiological contributions to coronary basal tone, including Ca 2ϩ -activated K ϩ currents (4,5). Studies utilizing large-animal models to address pressure overload LV hypertrophy and its role in the development of HF are currently lacking (14).…”