PT  - JOURNAL ARTICLE
AU  - Asano, Shinichi
AU  - Bratz, Ian N.
AU  - Berwick, Zachary C.
AU  - Fancher, Ibra S.
AU  - Tune, Johnathan D.
AU  - Dick, Gregory M.
TI  - Penitrem A as a Tool for Understanding the Role of Large Conductance Ca<sup>2+</sup>/Voltage-Sensitive K<sup>+</sup> Channels in Vascular Function
AID  - 10.1124/jpet.111.191072
DP  - 2012 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 453--460
VI  - 342
IP  - 2
4099  - http://jpet.aspetjournals.org/content/342/2/453.short
4100  - http://jpet.aspetjournals.org/content/342/2/453.full
SO  - J Pharmacol Exp Ther2012 Aug 01; 342
AB  - Large conductance, Ca2+/voltage-sensitive K+ channels (BK channels) are well characterized, but their physiological roles, often determined through pharmacological manipulation, are less clear. Iberiotoxin is considered the “gold standard” antagonist, but cost and membrane-impermeability limit its usefulness. Economical and membrane-permeable alternatives could facilitate the study of BK channels. Thus, we characterized the effect of penitrem A, a tremorigenic mycotoxin, on BK channels and demonstrate its utility for studying vascular function in vitro and in vivo. Whole-cell currents from human embryonic kidney 293 cells transfected with hSlo α or α + β1 were blocked >95% by penitrem A (IC50 6.4 versus 64.4 nM; p < 0.05). Furthermore, penitrem A inhibited BK channels in inside-out and cell-attached patches, whereas iberiotoxin could not. Inhibitory effects of penitrem A on whole-cell K+ currents were equivalent to iberiotoxin in canine coronary smooth muscle cells. As for specificity, penitrem A had no effect on native delayed rectifier K+ currents, cloned voltage-dependent Kv1.5 channels, or native ATP-dependent KATP current. Penitrem A enhanced the sensitivity to K+-induced contraction in canine coronary arteries by 23 ± 5% (p < 0.05) and increased the blood pressure response to phenylephrine in anesthetized mice by 36 ± 11% (p < 0.05). Our data indicate that penitrem A is a useful tool for studying the role of BK channels in vascular function and is practical for cell and tissue (in vitro) studies as well as anesthetized animal (in vivo) experiments.