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Inward‐Rectifier K + Channels in Vascular Smooth Muscle Prevent Myogenic Tone Development in Mouse Bladder Arterioles
Author(s) -
Tykocki Nathan,
Heppner Thomas,
Bonev Adrian,
Nelson Mark
Publication year - 2015
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.29.1_supplement.637.3
Subject(s) - chemistry , myogenic contraction , arteriole , bk channel , iberiotoxin , microcirculation , medicine , depolarization , phenylephrine , hyperpolarization (physics) , anatomy , endocrinology , inward rectifier potassium ion channel , vascular smooth muscle , apamin , vasodilation , biophysics , membrane potential , potassium channel , blood pressure , smooth muscle , biology , ion channel , biochemistry , receptor , organic chemistry , nuclear magnetic resonance spectroscopy
The urinary bladder is highly vascularized, and chronic decreases in blood flow are linked to bladder dysfunction. While increases in intraluminal pressure constrict most arterioles (“myogenic tone”), the regulation of bladder vascular diameter is largely unknown. We examined the myogenic and vasoactive properties of mouse bladder feed arterioles to determine how they affect bladder blood flow. Myogenic tone was wholly absent from isolated pressurized bladder arterioles (5‐80 mmHg). This was endothelium‐independent, as inhibition of eNOS (100 µM LNNA) and K Ca channels (300 nM apamin and 100 nM charybdotoxin) did not alter diameter. However, arterioles constricted to U‐46619 (1 µM), phenylephrine (10 μM) and depolarizing stimuli (60 mM K + ). Pre‐constricted arterioles dilated to carbachol (1 µM) and the IK/SK opener NS309 (1 µM), but not the TRPV4 agonist GSK1016790A (100 nM). The inward‐rectifier K + (K IR ) channel blockers BaCl 2 (100 μM) and ML‐133 (5 µM) caused significant constriction, indicative of K IR channel activity. Electrophysiological recordings from isolated bladder arteriolar smooth muscle cells showed significant Ba 2+ ‐sensitive inward currents characteristic of K IR channels, and typical K V channel currents. Furthermore, bladder arterioles from smooth muscle‐specific K IR 2.1 knockout mice developed significant myogenic tone at 60 and 80 mmHg. Together, these data support the concept that the absence of pressure‐induced depolarizing conductances leads to K IR channel activation, which then causes membrane hyperpolarization and dilation. This represents a novel mechanism in bladder arterioles that opposes myogenic constriction to maintain blood flow during filling. Supported by NIH R37DK053832.