Faculty Collaboration Database

Reversal of hypothermia-induced action potential lengthening by the KATP channel agonist bimakalim in isolated guinea pig ventricular muscle. Gen Pharmacol 1998 Jul;31(1):125-31

Date

05/22/1998

Pubmed ID

9595290

DOI

10.1016/s0306-3623(97)00395-9

Scopus ID

2-s2.0-0032127418 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

1. ATP-sensitive potassium (KATP) channel openers shorten cardiac ventricular muscle action potential duration (APD), reduce resting and developed contractile force, and have been shown to provide cardioprotection when given before, during, and after either short-term ischemia or long-term hypothermia. The authors' aim was to determine the concentration-dependent effect of the potent KATP channel opener bimakalim on transmembrane action potential changes induced by mild (27 degrees C) and moderate (20 degrees C) hypothermia in isolated guinea pig ventricular muscle. 2. Conventional microelectrode techniques were used to record action potentials (APs) in single myocytes during normothermia (37 degrees C) and hypothermia in the presence and absence of 0.1 to 30 mumol.l-1 bimakalim. 3. Hypothermia alone increased APD and depolarized the diastolic membrane potential (DMP): APD90 = 141.7 +/- 7.0 msec and DMP -86.2 +/- 1.4 mV (n = 6) at 37 degrees C versus 235.7 +/- 7.8 msec and -75.6 +/- 1.0 mV at 20 degrees C (n = 7). At 37 degrees C, bimakalim (0.1-10 mumol.l-1) shortened APD in a concentration-dependent fashion. 4. APD90 was markedly reduced from 141.7 +/- 7.0 msec without bimakalim to 9.5 +/- 2.6 msec with 10 mumol.l-1 bimakalim (n = 6); this effect was blocked by glibenclamide. DMP was hyperpolarized by bimakalim. More bimakalim was required to shorten APs during mild and moderate hypothermia. The 50% effective concentration (EC50) of bimakalim required to maximally shorten APD90 was 0.96 +/- 0.10 mumol.l-1 at 37 degrees C; this increased to 3.96 +/- 0.24 mumol.l-1 at 27 degrees C, and to 12.34 +/- 0.72 mumol.l-1 at 20 degrees C. Relative to hypothermia-induced depolarization, bimakalim hyperpolarized DMP toward drug-free values obtained at 37 degrees C. 5. These results indicate that hypothermia shifts the bimakalim concentration APD90 response curve to the right such that 13 times more bimakalim is required at 20 degrees C shorten APD by the same amount as at 37 degrees C. Bimakalim also reverses hypothermia-induced AP lengthening and tends to reverse the hypothermia-induced decrease in DMP. 6. These findings aid in our understanding of the cardioprotective effects of KATP channel openers during hypothermia.

Author List

Lathrop DA, Contney SJ, Bosnjak ZJ, Stowe DF

Authors

Zeljko Bosnjak PhD, MS Emeritus Professor in the Medicine department at Medical College of Wisconsin
David F. Stowe PhD, MA, MA Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Benzopyrans
Body Temperature Regulation
Dihydropyridines
Electric Stimulation
Guinea Pigs
Heart Ventricles
In Vitro Techniques
Papillary Muscles
Potassium Channels
Temperature