Inhibition of vascular smooth muscle inward-rectifier K⁺channels restores myogenic tone in mouse urinary bladder arterioles

Abstract

Tykocki NR, Bonev AD, Longden TA, Heppner TJ, Nelson MT. Inhibition of vascular smooth muscle inward-rectifier K ϩ channels restores myogenic tone in mouse urinary bladder arterioles.

Dystrophin is expressed in smooth muscle and afferent nerve fibers in the rat urinary bladder

“…The role of the vasculature in bladder function is not entirely clear because it has received relatively little scientific attention. Nevertheless, Tycocki and colleagues found that myogenic tone in mouse bladder arterioles is attributable to the activity of smooth muscle inward rectifying potassium channels (K IR ) for the control of bladder blood flow. As dystrophin has been shown to serve as an anchor for K IR , specifically K IR 2.1, in mouse cardiomyocytes, a similar role for dystrophin may be present in the bladder vasculature.…”

Perivascular adipose tissue and the dynamic regulation of Kv7 and Kir channels: Implications for resistant hypertension

“…K ir 2.1 is the predominantly expressed K ir subunit in VSMCs encoded by the KCNJ2 gene; K ir 2.2 has also been observed at the mRNA level in key vascular beds . A functional role of these VSMC K + channels has been reported in cerebral, coronary, skeletal muscle arteries and renal, urinary bladder arterioles . Smooth muscle K ir channels are predominately described in smaller resistance vessels where they influence resting membrane potential; they appear functionally absent from larger vessels .…”

Potential vascular mechanisms in an ex vivo functional pig bladder model

“…While investigating the underlying mechanisms of vascular tonic regulation, Tykocki recently discovered that feed arterioles lacked myogenic tone over a wide range of physiologic pressures in the mouse urinary bladder. 24 Similar studies in other animal models are lacking; however, if such processes are also absent in other species, it emphasizes the importance of a metabolic or endothelial response in the proposed autoregulatory mechanism. The choice to utilize a porcine model has proven to be advantageous in biomedical study due to the anatomic and physiologic (including lifespan) similarities shared with humans compared to other animal models.…”

“…Although our study suggests the potential for an intrinsic autoregulatory mechanism in the bladder, the nature of this mechanism remains unclear. While investigating the underlying mechanisms of vascular tonic regulation, Tykocki recently discovered that feed arterioles lacked myogenic tone over a wide range of physiologic pressures in the mouse urinary bladder . Similar studies in other animal models are lacking; however, if such processes are also absent in other species, it emphasizes the importance of a metabolic or endothelial response in the proposed autoregulatory mechanism.…”