Large conductance, Ca-activated K channels (BKCa) and arteriolar myogenic signaling |
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Authors: | Michael A Hill Yan Yang Michael J Davis Andrew P Braun |
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Institution: | a Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, USA b Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65211, USA c Department of Biological Engineering, University of Missouri, Columbia, MO 65211, USA d Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada AB T2N 4N1 |
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Abstract: | Myogenic, or pressure-induced, vasoconstriction is critical for local blood flow autoregulation. Underlying this vascular smooth muscle (VSM) response are events including membrane depolarization, Ca2+ entry and mobilization, and activation of contractile proteins. Large conductance, Ca2+-activated K+ channel (BKCa) has been implicated in several of these steps including, (1) channel closure causing membrane depolarization, and (2) channel opening causing hyperpolarization to oppose excessive pressure-induced vasoconstriction. As multiple mechanisms regulate BKCa activity (subunit composition, membrane potential (Em) and Ca2+ levels, post-translational modification) tissue level diversity is predicted. Importantly, heterogeneity in BKCa channel activity may contribute to tissue-specific differences in regulation of myogenic vasoconstriction, allowing local hemodynamics to be matched to metabolic requirements. Knowledge of such variability will be important to exploiting the BKCa channel as a therapeutic target and understanding systemic effects of its pharmacological manipulation. |
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Keywords: | BKCa large conductance Ca2+-activated K+ channel CICR Ca2+-induced Ca2+ release EC endothelial cell Em membrane potential IBTX iberiotoxin IK intermediate conductance Ca2+-activated K+ channel IP3 inositol triphosphate MLC myosin light chain PIP2 phosphatidylinositol 4 5-bisphosphate PLC Phospholipase C RCK regulator of conductance for K+ ROS reactive oxygen species RyR ryanodine receptor SK small conductance Ca2+-activated K+ channel SR sarcoplasmic reticulum STOC spontaneous transient outward current STREX STRess axis regulated EXon VGCC voltage-gated Ca2+ channel VSD voltage sensor domain VSM vascular smooth muscle |
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