Proceedings of The Physiological Society

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB186

Poster Communications

Further investigation into the role of Kv7 channels in +

K. S. Jahan1, J. B. Stott1, I. A. Greenwood1

1. St George's University of London, London, United Kingdom.

Recently KCNQ encoded Kv7 channels have been identified in vascular smooth muscle cells, where they are responsible for maintaining resting membrane potential and vascular tone (1). Moreover, Kv7 channels contribute to β-adrenoceptor mediated vasodilation in renal arteries and that this is down-regulated in hypertension (2). However, the exact mechanism of β- adrenoceptor mediated Kv7 channel activation is still unknown. Therefore, this study aims to determine the relationship between β- adrenoceptors and Kv7 channel activation in renal arteries.Isometric tension recordings were conducted on renal arteries of male wistar rats (200-225g). Three β-adrenoceptor agonists, isoprenaline (mixed β), dobutamine (β1 selective) and salbutamol (β2 selective), were added cumulatively (1nM -10 μM) to vessels pre-constricted with 3µM methoxamine in the presence/absence of the Kv7 blocker linopirdine, the βγ subunit inhibitor gallein or DMSO (control). All data are expressed as mean ± S.E.M and compared by two-way ANOVA followed by Bonferroni post-hoc, unless otherwise stated. Isoprenaline, dobutamine, and salbutamol induced concentration dependant relaxation of pre-constricted renal arteries. Application of 3μM linopirdine caused renal arteries to constrict, and produced a mean contraction (relative to 60mM KCl induced response) of 61.49 ± 15.03%, compared with 0% in time matched controls (n=5; p<0.05 (analysed by paired student t-test)) and significantly inhibited isoprenaline mediated relaxations (reduction in Emax from 79.72 ± 6.28% to 9.46 ± 5.90% (n=6; p<0.0001)) as well as dobutamine and salbutamol mediated relaxations (Emax decreased from 90.33 ± 5.00% to 25.2 ± 12.12% (n=5; p<0.0001) and 93.99± 4.7% to 16.50± 7.68% (n=4; p<0.0001), respectively). Application of gallein constricted renal arteries with a mean contraction relative to 60mM KCl induced response of 89.08 ± 1.84% (n=6). Gallein also inhibited β-adrenoceptor mediated relaxation of renal arteries and caused Emax to decrease from 76.48 ± 4.80% to 14.02 ± 10.01% (n=6; p<0.0001) for isoprenaline-mediated relaxations, from 96.25 ± 3.25% to 18.21 ± 12.20% (n=4; p<0.0001) for dobutamine mediated relaxations, and from 82 ± 10.65% to 6.50 ± 4.24% (n=4; p<0.0001) for salbutamol mediated relaxations. This work supports previous findings, which show that Kv7 channels are involved in mediating β-adrenoceptor relaxation of renal arteries. This study also shows that βγ subunit translocation is involved in β-adrenoceptor mediated relaxation of renal arteries. This suggests a potential role for βγ subunits in Kv7 channel activation in the rat renal artery.

Where applicable, experiments conform with Society ethical requirements