Vasorelaxation by hydrogen sulphide involves activation of Kv7 potassium channels

Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide-Induced Relaxation of Rat Mesenteric Small Arteries

“…Our findings support the previous observations; at pH 7.4 the H 2 S levels were below the detection limit of the electrode, although GYY4137 causes relaxation equipotent to that induced by the NaHS and Na 2 S salts in mesenteric arteries. Together with the observation that L-cysteine is required to measure the release of H 2 S (Martelli et al, 2013), our findings suggest that the GYY4137-induced release of free H 2 S may also depend on the presence of tissue thiols or it only releases other sulfide species (e.g., HS 2 and S 22 ). Moreover, it should be explored whether a sulfide-independent mechanism may contribute to GYY4137 relaxations.…”

“…Opening of potassium (K) channels leads to hyperpolarization and closing of voltagedependent Ca 21 -channels, decreasing the intracellular calcium concentration ([Ca 21 ] i ), followed by vasodilation. Several studies have shown that H 2 S opens ATP-sensitive potassiumchannels (K ATP channels), leading to hyperpolarization of the vascular smooth muscle layer (Zhao and Wang, 2002;Tang et al, 2005;Webb et al, 2008;Martelli et al, 2013). Although opening of K ATP channels has been widely accepted as a main mechanism underlying H 2 S-induced vasorelaxation, some studies have found only a small or no involvement of K ATP channels (Kubo et al, 2007;Kiss et al, 2008;Cheang et al, 2010).…”

“…Although opening of K ATP channels has been widely accepted as a main mechanism underlying H 2 S-induced vasorelaxation, some studies have found only a small or no involvement of K ATP channels (Kubo et al, 2007;Kiss et al, 2008;Cheang et al, 2010). Other potassium channels (K channels) have also been reported to play a role in H 2 S relaxation such as voltage-gated K channels (Cheang et al, 2010), K V 7 channels (Schleifenbaum et al, 2010;Martelli et al, 2013;Hedegaard et al, 2014), and large conductance calcium-activated potassium channels (BK Ca ) (Jackson-Weaver et al, 2011Li et al, 2012). It has been shown that the H 2 S donors NaHS and Na 2 S activate calcium sparks (Liang et al, 2012;Jackson-Weaver et al, 2013) and also that they reduce global [Ca 21 ] in cerebral arterioles (Liang et al, 2012).…”

The novel H 2 S-donor 4-carboxyphenyl isothiocyanate promotes cardioprotective effects against ischemia/reperfusion injury through activation of mitoK ATP channels and reduction of oxidative stress

“…1) is a H 2 S-releasing compound, known to evoke vasorelaxing responses in isolated rat aorta and to increase coronary flow in isolated rat hearts [23]. Moreover, 4CPI was shown to cause membrane hyperpolarization in human aortic smooth muscle cells through the activation of Kv7 potassium channels, which play a role in H 2 Sinduced vasodilation [24]. Noteworthy, Kv7 channels (in particular, Kv7.4) have been recently recognized in heart mitochondria, where they appear to play a cardioprotective role [25].…”

Subtype-Selective Activation of Kv7 Channels by AaTXKβ(2–64), a Novel Toxin Variant from theAndroctonus australisScorpion Venom

“…K v 7.4 channels are expressed in central auditory pathways and in inner ear sensory hair cells (Kubisch et al, 1999), in skeletal muscle cells (Iannotti et al, 2013), and in smooth muscle cells of the gastrointestinal tract (Jepps et al, 2009;Ipavec et al, 2011). In blood vessels, K v 7.4 channels contribute to vascular reactivity to vasopressors and vasodilators (Yeung et al, 2007;Mani and Byron, 2011;Martelli et al, 2013), and down-regulation of K v 7.4 contributes to primary and secondary hypertension (Jepps et al, 2011). K v 7.5 subunits are expressed in neurons, showing a distribution that largely overlaps those of K v 7.2 and K v 7.3, and are thought to contribute to I KM heterogeneity (Schroeder et al, 2000); K v 7.5 transcripts and/or proteins have been also identified in skeletal and smooth muscle cells .…”