Abstract
KCNQ-encoded voltage-gated potassium channels (Kv7) have recently been identified as key regulator of vascular and non-vascular smooth muscle tone. Kv7 channel subtypes (Kv7.1-Kv7.5) have a specific tissue distribution and pathophysiological role. Loss of function mutations in four of the five KV7 genes lead to distinct inherited diseases, such as cardiac arrhythmias, epilepsy and sensorineuronal deafness. However, their physiological role in corporal smooth muscle (CSM) remains to be fully elucidated. In this study, we examined the molecular expression and functional role of Kv7 channels in corporal smooth muscle. Expression of KCNQ isoforms in human corporal smooth muscle (hCSM) cells was examined using RT-PCR. Functional responses to Kv7 channel modulators were evaluated in normal and diabetic (DM) rabbit corporal smooth muscle (CSM) tissue. Isolated CSM strips were mounted in an organ-bath system, and the relaxation effects of the following Kv7 channel subtype selective activators: ML213 (Kv7.2/Kv7.4channels), ML277 (Kv7.1) and ICA 069673 (Kv7.2/7.3), Flupirtine (Kv7.2–7.5 channels) were evaluated by cumulative addition to strips pre-contracted with10-5 M phenylephrine (PE). Fluo-4 fluorescence techniques were used to monitor changes in [Ca2+]cyt.
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