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BK channel function, venous tone and blood pressure regulation
Author(s) -
Xu Hui,
Kandlikar Sachin
Publication year - 2009
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.23.1_supplement.1018.1
Subject(s) - bk channel , iberiotoxin , mean circulatory filling pressure , chemistry , mesenteric arteries , medicine , vascular smooth muscle , potassium channel , anatomy , calcium activated potassium channel , endocrinology , biophysics , anesthesia , blood pressure , biology , artery , central venous pressure , heart rate , smooth muscle
Impaired large‐conductance Ca 2+ ‐activated K + (BK) channel function in smooth muscle cells (SMC) causes an increase in intracellular Ca 2+ and vascular tone in arteries in hypertension. There have been few studies of BK channel function in venous SMC. Venomotor tone contributes to blood pressure (BP) regulation and increased venomotor tone occurs in human and experimental hypertension. Venous SMC BK channel function was studied using molecular, cellular and integrative approaches in normotensive rats. Unitary BK currents were recorded using inside‐out patches of myocytes from acutely isolated mesenteric veins (MV) SMCs. Currents were sensitive to voltage and [Ca 2+ ] i . Whole cell recordings from MV SMCs revealed spontaneous transient outward currents (STOCs). STOCs were blocked by TEA (1 mM) indicating that BK channels are functional in MV SMCs. Immunocytochemical and Western blot techniques confirmed the presence of BK channel α‐ and β1‐subunits in MV SMCs. Ex vivo studies of the exposed mesentery of anesthetized rats revealed that local block of BK channels by iberiotoxin (IBTX, 100 nM) caused greater constriction of MV compared to mesenteric arteries (MA). Acute inhibition of BK channels with IBTX (0.3 μM/kg, iv) in vivo increased arterial BP and reduced venous capacitance, measured as an increase in mean circulatory filling pressure (MCFP) in conscious rats. Increased MCFP caused by IBTX was more sustained than the increase in arterial BP. These data show that MV SMCs express functional BK channels which regulate venous tone. BK channels play a larger role in regulation of MV than MA tone. These data also show for the first time that BK channels contribute to the regulation of venous tone in vivo , since acute blockade with IBTX increased MCFP. (Supported by P01 HL070687)