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Ca V 3.2 knockout mice display enhanced myogenic tone due to reduced BK Ca ‐mediated feedback (1077.3)
Author(s) -
Harraz Osama,
Brett Suzanne,
Wilson Sean,
Welsh Donald
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1077.3
Subject(s) - electrical impedance myography , chemistry , mesenteric arteries , ryanodine receptor , transient receptor potential channel , myogenic contraction , vasoconstriction , bk channel , electrophysiology , endocrinology , anatomy , medicine , vascular smooth muscle , biophysics , constriction , vasodilation , receptor , smooth muscle , calcium , biology , artery , biochemistry
In resistance arteries, there is an emerging view that Ca V 3.2 channel restrains vascular constriction through a feedback response that involves ryanodine receptors (RyR), Ca 2+ spark generation and the modulation of large‐conductance Ca 2+ activated K + channel (BK Ca ). In the present study, we tested this hypothesis by examining the vasomotor, electrophysiological and Ca 2+ responses of mesenteric arterial smooth muscle isolated from wild type (WT) and Ca V 3.2 knockout (KO) mice. Using vessel myography, we first observed enhanced myogenic tone in KO arteries, a finding consistent with the loss of feedback response. Control myography and electrophysiological experiments subsequently confirmed the inability of Ni 2+ (Ca V 3.2 blocker) to either constrict arteries or suppress T‐type currents in KO tissues. Line scan analysis, performed on opened arteries loaded with fluo‐4, illustrated the presence of Ca 2+ sparks in all arteries with the subsequent application of Ni 2+ only affecting WT arteries. Consistent with Ca 2+ imaging, the frequency of BK Ca ‐induced spontaneous transient outward currents (STOC) dropped in WT but not KO cells upon the pharmacological suppression of Ca V 3.2 channel. Overall, our findings support the view that Ca V 3.2 channels drive a local Ca 2+ ‐induced Ca 2+ release‐like process that restrains arterial constriction through the induction of Ca 2+ sparks and the activation of BK Ca channels.