Research ArticleVASCULAR BIOLOGY

Microtubule structures underlying the sarcoplasmic reticulum support peripheral coupling sites to regulate smooth muscle contractility

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Sci. Signal.  19 Sep 2017:
Vol. 10, Issue 497, eaan2694
DOI: 10.1126/scisignal.aan2694

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Supporting ion channel coupling in smooth muscle

Cerebral resistance arteries must autoregulate their vascular tone to maintain a constant supply of blood flow to the brain regardless of fluctuations in blood pressure. Vasoconstriction of arterial smooth muscle is initiated by Ca2+ influx through plasma membrane channels, which also triggers type 2 ryanodine receptors (RyR2s) in the sarcoplasmic reticulum to generate Ca2+ sparks. This process balances vasoconstriction by causing vasodilation, which results from the activation of BK channels in the plasma membrane by Ca2+ sparks. Pritchard et al. found that arching microtubule structures maintained the close opposition of the sarcoplasmic reticulum and the plasma membrane at regions called peripheral coupling sites. In rodent cerebral arteries, pharmacological disruption of microtubule networks caused the sarcoplasmic reticulum and plasma membrane at these sites to move farther apart, spread out the Ca2+ sparks over a greater area, decreased BK channel activity, and impaired the ability of cerebral arteries to autoregulate vascular tone. These effects were not seen upon disruption of the actin cytoskeleton. Thus, microtubules play a critical structural role in smooth muscle in ensuring the functional coupling of the activities of RyR2s in the sarcoplasmic reticulum and BK channels in the plasma membrane.