Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 134, Issue 2, Pages 247-256Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjp.0704270
Keywords
myogenic reactivity; arteriolar smooth muscle; capacitative Ca2+ entry; IP3 receptor; cell signalling
Categories
Ask authors/readers for more resources
1 Arteriolar myogenic tone shows a marked dependency on extracellular Ca-2 (+). The contribution played by mechanisms such as intracellular Ca2 + release and capacitative entry, however, are less certain. The present studies aimed to demonstrate functional evidence for involvement of such mechanisms in myogenic tone and reactivity. 2 Single cremaster arterioles were denuded of endothelium, pressurized under no-flow conditions and loaded with fura 2-AM for measurement of changes in intracellular Ca-2 ' [Ca2 +](i). The cell permeable, putative, IP3 receptor antagonist 2APB (2 aminoethoxydiphenyl borate) was used to determine the possible role Of IP3 receptor-mediated mechanisms in arteriolar myogenic tone and reactivity. 3 Arterioles dilated in response to increasing concentrations of 2APB (1 - 300 muM) without a concomitant change in global [Ca2 +](i). Also 2APB (50 muM) completely inhibited the myogenic constriction in response to a step change in luminal pressure (50 - 120 mmHg) with no apparent effect on pressure-mediated increases in [Ca2 +](i). 2APB markedly attenuated the constrictor response and [Ca2 +](i) increase stimulated by phenylephrine but not KC1. 4 Capacitative Ca2 + influx in arterioles was demonstrated either by re-addition of extracellular [Ca2 +] following pre-treatment with 1 or 10 muM nifedipine in Ca2 + free buffer or exposure of vessels to thapsigargin (1 muM) to induce store depletion. In both cases 2APB inhibited the increase in [Ca2 +](i). Capacitative Ca2 + entry showed an inverse relationship with intraluminal pressure over the range 10 - 120 mmHg. 5 Consistent with an effect on a Ca2 + entry pathway, 2APB had no effect on intracellular (caffeine releasable) Ca2 + stores while decreasing the rate of Mn2 + quench of fura 2 fluorescence. 6 The results provide functional evidence for capacitative Ca2 + entry in intact arteriolar smooth muscle. The effectiveness of 2APB in inhibiting both non-voltage gated Ca2 + entry and responsiveness to an acute pressure step is consistent with the involvement of an axis involving IP3-mediated and or capacitative Ca2 + entry mechanisms in myogenic reactivity. Given the lack of effect of 2APB on pressure-induced changes in global [Ca2 +](i) it is suggested that such mechanisms participate on a localized level to couple the myogenic stimulus to contraction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available