Atrophic limbs exhibit decreased blood flow and histological changes in the arteries perfusing muscles. However, the effect of atrophy on vascular smooth muscle function is poorly understood. Here, we investigated the effect of unilateral sciatic denervation on the myogenic response (MR) and the ionic currents in deep femoral artery (DFA) smooth muscles from Sprague-Dawley rats. Because denervated rats were capable of treadmill exercise (20 m/min, 30 min, 3 times/wk), the impact of exercise training on these effects was also assessed. Skeletal arteries were harvested 3 or 5 wk after surgery. Then skeletal arteries or myocytes were subjected to video analysis of pressurized artery, myography, whole-cell patch clamp, and real-time quantitative PCR to determine the effect of hindlimb paralysis in the presence/absence of exercise training on MR, contractility, ionic currents, and channel transcription, respectively. In sedentary rats, atrophy was associated with loss of MR in the DFA at 5 wk. The contralateral DFA had a normal MR. At 5 wk after surgery, DFA myocytes from the atrophic limbs exhibited depressed L-type Ca2+ currents, GTPγS-induced transient receptor potential cation channel (TRPC)-like currents, 80 mM KCl-induced vasoconstriction, TRPC6 mRNA, and voltage-gated K+ and inwardly rectifying K+ currents. Exercise training abrogated the differences in all of these functions between atrophic side and contralateral side DFA myocytes. These results suggest that a probable increase in hemodynamic stimuli in skeletal artery smooth muscle plays an important role in maintaining MR and ionic currents in skeletal artery smooth muscle. This may also explain the observed benefits of exercise in patients with limb paralysis. NEW & NOTEWORTHY Myogenic responses (MRs) in rat skeletal arteries feeding the unilateral atrophic hindlimb were impaired. In addition, the L-type Ca2+ channel current, the TRPC6-like current, and TRPC6 mRNA levels in the corresponding myocytes decreased. Voltage-gated K+ channel currents and inwardly rectifying K+ channel currents were also attenuated in atrophic side myocytes. Exercise training effectively abrogated electrophysiological dysfunction of atrophic side myocytes and prevented loss of the MR.
Arterioles and small arteries change their tone in response to transmural pressure changes, called myogenic tone (MT). In comparison to the branches of cerebral arteries (CA) showing prominent MT, the third branches of mesenteric arteries (MA) with similar diameters show weaker MT. Here, we aimed to analyze the electrophysiological differences responsible for the weaker MT in MA (MTMA) than MT in CA (MTCA). We measured ionic current using patch clamp in isolated MA smooth muscle cells (MASMCs) and CA smooth muscle cells (CASMCs) of rats. MT was analyzed using video analysis of pressurized small arteries. Quantitative‐PCR (q‐PCR) and immunofluorescence confocal microscopy were used to compare the mRNA and protein expression level of big‐conductance Ca2+‐activated K+ channel (BKC a) subunits (Slo1α and Sloβ1). Whole‐cell patch clamp study revealed higher density of voltage‐operated Ca2+ channel current (IC aV) in the MASMCs than in CASMCs. Although voltage‐gated K+ channel current (IK v) was also higher in MASMCs, treatment with Kv inhibitor (4‐aminopyridine) did not affect MTMA. Interestingly, BKC a current density and the frequency of spontaneous transient outward currents (STOCs) were consistently higher in MASMCs than in CASMCs. Inside‐out patch clamp showed that the Ca2+‐sensitivity of BKC a is higher in MASMCs than in CASMCs. Iberiotoxin, a selective BKC a inhibitor, augmented MTMA by a larger extent than MTCA. Although q‐PCR analysis did not reveal a significant difference of mRNAs for Slo1α and Sloβ1, immunofluorescence image suggested higher expression of Slo1α in MASMCs than in CASMCs. Despite the large IC aV density, the high activities of BKC a including the more frequent STOCs in MASMCs veils the potentially strong MTMA.
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