RT Journal Article
SR Electronic
T1 Activation of Cardiac ATP-Sensitive K<sup>+</sup> Channels by KRN4884, a Novel K<sup>+</sup> Channel Opener
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 770
OP 777
VO 283
IS 2
A1 Atsushi Shinbo
A1 Kyoichi Ono
A1 Toshihiko Iijima
YR 1997
UL http://jpet.aspetjournals.org/content/283/2/770.abstract
AB In the present study, we have investigated the mechanism underlying the activation by 5-amino-N-[2-(2-chlorophenyl)ethyl]-N′-cyano-3-pyridinecarboxamidine (KRN4884), a new K+ channel opener, of ATP-sensitive K+ (KATP) channels in single ventricular cells of guinea pig hearts by the inside-out patch-clamp method. In the presence of intracellular ATP (1 mM), KRN4884 (0.1–3 μM) activated KATP channels in a concentration-dependent manner (EC50 = 0.55 μM) without affecting the unitary current conductance and the gating properties. KRN4884 (0.3 μM) shifted the concentration-response relationship for ATP-induced KATPchannel inhibition to the right and slightly upward direction without altering the slope. After either the spontaneous or Ca++-induced channel rundown, KRN4884 (1 and 3 μM) partially restored the KATP channel activity. Furthermore, the effect of KRN4884 was augmented by the presence of uridine 5′-diphosphate (3 mM). The results indicate that KRN4884 activates cardiac KATP channels through not only decreasing the sensitivity of the channel to ATP but also directly stimulating the opening of the channel. The American Society for Pharmacology and Experimental Therapeutics