Zinc pyrithione activates K+ channels and hyperpolarizes the membrane of rat pulmonary artery smooth muscle cells

PloS One
Basma G Eid, Alison M Gurney

Abstract

The membrane potential helps determine pulmonary artery smooth muscle cell (PASMC) contraction. The Kv7 channel activators, retigabine and flupirtine, are thought to dilate pulmonary arteries by hyperpolarising PASMC. Zinc pyrithione activates Kv7 channels by a mechanism distinct from retigabine and with different Kv7 subunit selectivity. This study aimed to determine if zinc pyrithione selectively activates Kv7 channels in rat PASMC to evoke pulmonary artery dilation. Zinc pyrithione relaxed pulmonary arteries with half-maximal effect at 4.3μM. At 10μM it activated pronounced voltage-dependent K+ current and hyperpolarized PASMCs by around 10mV. Tetraethylammonium ions (TEA, 10mM) and paxilline (1μM) abolished both the current and hyperpolarisation. XE991 (10μM) blocked the hyperpolarization and reduced the current by 30%. Iberiotoxin (50nM) had no effect on the hyperpolarisation, but reduced the current by 40%. The XE991-sensitive current activated with an exponential time course (time constant 17ms), whereas the iberiotoxin-sensitive current followed a bi-exponential time course (time constants 6 and 57ms), suggesting that the drugs blocked different components of the zinc pyrithione-induced current. Zinc pyrithione therefor...Continue Reading

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Citations

Mar 19, 2019·British Journal of Pharmacology·Gema Mondéjar-ParreñoAngel Cogolludo
Jul 18, 2020·Frontiers in Physiology·Gema Mondejar-ParreñoAngel Cogolludo
Jun 3, 2021·Nature Communications·Ashenafi H BetrieScott Ayton

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