Myogenic contraction in rat skeletal muscle arterioles:: smooth muscle membrane potential and Ca2+ signaling

The present studies examined relationships between intraluminal pressure, membrane potential (E-m), and myogenic tone in skeletal muscle arterioles. Using pharmacological interventions targeting Ca2+ entry/release mechanisms, these studies also determined the role of Ca2+ pathways and E-m 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 E-m. Thus, despite further depolarization, at pressures >70 mmHg, little additional vasoconstriction occurred. This was not due to an inability of voltage-operated Ca2+ channels to be activated as KCl (75 mM) evoked depolarization and vasoconstriction at 120 mmHg. Nifedipine (1 mu M) and cyclopiazonic acid (30 mu M) significantly attenuated established myogenic tone, whereas inhibition of inositol 1,4,5-trisphosphate-mediated Ca2+ release/entry by 2-aminoethoxydiphenylborate (50 mu M) had little effect. Combinations of the Ca2+ entry blockers with the sarcoplasmic reticulum (SR) inhibitor caused a total loss of tone, suggesting that while depolarization-mediated Ca2+ entry makes a significant contribution to myogenic tone, an interaction between Ca2+ entry and SR Ca2+ release is necessary for maintenance of myogenic constriction. In contrast, none of the agents, in combination or alone, altered E-m, demonstrating the downstream role of Ca2+ mobilization relative to changes in E-m. Large-conductance Ca2+-activated K+ channels modulated E-m to exert a small effect on myogenic tone, and consistent with this, skeletal muscle arterioles appeared to show an inherently steep relationship between E-m and extent of myogenic tone. Collectively, skeletal muscle arterioles exhibit complex relationships between E-m, Ca2+ availability, and myogenic constriction that impact on the tissue's physiological function.