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1 School of Medical Sciences, RMIT University, Melbourne, Victoria, Australia
2 School of Medical Sciences, RMIT University, Melbourne, Victoria, Australia; Physiology and Pharmacology, University of New South Wales, Sydney, New South Wales, Australia
* To whom correspondence should be addressed. E-mail: michael.hill{at}unsw.edu.au.
The present studies examined relationships between intraluminal pressure, membrane potential (Em) 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 Em in determining steady state myogenic constriction. Studies were conducted in isolated and cannulated arterioles under zero flow. Increasing intraluminal pressure (0-150mmHg) resulted in progressive membrane depolarisation (-55.3 ± 4.1 to -29.4 ± 0.7mV) that exhibited a sigmoidal relationship between extent of myogenic constriction and Em. Thus, despite further depolarisation, at pressures >70mmHg, little additional vasoconstriction occurred. This was not due to an inability of voltage-operated Ca2+ channels to be activated as KCl (75µM) evoked depolarisation and vasoconstriction at 120mmHg. Nifedipine (1µM) and cyclopiazonic acid (30µM) significantly attenuated established myogenic tone whereas inhibition of IP3-mediated Ca2+ release/entry by 2-aminoethoxydiphenylborate (50µM) had little effect. Combinations of the Ca2+ entry blockers with the SR inhibitor caused a total loss of tone suggesting that while depolarisation-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 Em demonstrating the downstream role of Ca2+ mobilization relative to changes in Em. Large conductance, Ca2+-activated, K+ channels modulated Em to exert a small effect on myogenic tone, compared to reports on cerebral vessels, suggesting vascular heterogeneity. Consistent with this, skeletal muscle arterioles appear to show a steeper inherent relationship between Em and extent of myogenic tone. Collectively skeletal muscle arterioles exhibit complex relationships between Em, Ca2+ availability and myogenic constriction that impact on the tissues physiological function.
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