Myogenic contraction in rat skeletal muscle arterioles: smooth muscle membrane potential and Ca signaling

Kotecha, Neela, and Michael A. Hill. Myogenic contraction in rat skeletal muscle arterioles: smooth muscle membrane potential and Ca signaling. Am J Physiol Heart Circ Physiol 289: H1326–H1334, 2005. First published April 29, 2005; doi:10.1152/ajpheart.00323.2005.—The present studies examined relationships between intraluminal pressure, membrane potential (Em), and myogenic tone in skeletal muscle arterioles. Using pharmacological interventions targeting Ca entry/ release mechanisms, these studies also determined the role of Ca pathways and Em in determining steady-state myogenic constriction. Studies were conducted in isolated and cannulated arterioles under zero flow. Increasing intraluminal pressure (0–150 mmHg) resulted in progressive membrane depolarization ( 55.3 4.1 to 29.4 0.7 mV) that exhibited a sigmoidal relationship between extent of myogenic constriction and Em. Thus, despite further depolarization, at pressures 70 mmHg, little additional vasoconstriction occurred. This was not due to an inability of voltage-operated Ca channels to be activated as KCl (75 mM) evoked depolarization and vasoconstriction at 120 mmHg. Nifedipine (1 M) and cyclopiazonic acid (30 M) significantly attenuated established myogenic tone, whereas inhibition of inositol 1,4,5-trisphosphate-mediated Ca release/entry by 2-aminoethoxydiphenylborate (50 M) had little effect. Combinations of the Ca entry blockers with the sarcoplasmic reticulum (SR) inhibitor caused a total loss of tone, suggesting that while depolarization-mediated Ca entry makes a significant contribution to myogenic tone, an interaction between Ca entry and SR Ca release is necessary for maintenance of myogenic constriction. In contrast, none of the agents, in combination or alone, altered Em, demonstrating the downstream role of Ca mobilization relative to changes in Em. Large-conductance Ca -activated K channels modulated Em to exert a small effect on myogenic tone, and consistent with this, skeletal muscle arterioles appeared to show an inherently steep relationship between Em and extent of myogenic tone. Collectively, skeletal muscle arterioles exhibit complex relationships between Em, Ca availability, and myogenic constriction that impact on the tissue’s physiological function.