The effects of K+ channels modulators terikalant and glibenclamide on membrane potential changes induced by hypotonic challenge of guinea pig ventricular myocytes.
Contribution of inward rectifier K(+) currents (I(K1)) and ATP-sensitive K(+) currents (I(KATP)) to membrane potential changes of ventricular myocytes appearing during hypotonic challenge is unclear. We used here the whole cell patch clamp technique, voltage and current clamp modes, to record membrane potentials and ionic currents in isolated guinea pig ventricular myocytes under isotonic or hypotonic perfusion. The difference in osmolarity between iso- and hypotonic solutions was about 100 mOsm. Exposure to hypotonic solution for 60 s induced initial prolongation of action potential duration at 90% of repolarization (APD(90)) (from 176 +/- 10 to 189 +/- 11 ms, P<0.05, n = 13). Further perfusion for the next 300 s shorthened APD(90) to 135 +/- 9 ms (P<0.01, in comparison with control values, n = 13) and depolarized resting potential from -79.2 +/- 1.5 to -75.0 +/- 0.9 mV, (P<0.05, n = 13). Neither pretreatment with a blocker of I(K1) channels, terikalant at 10 microM, nor with a blocker of I(KATP) channels, glibenclamide at 1 microM, prevented the above-mentioned changes in membrane potential induced by hypotonic challenge when a pipette solution containing 5 mM ATP was used. Also, glibenclamide and terikalant did not affect the hypotonic-sensitive current, obtained by ramp or voltage-step protocols, respectively. Additionally, the current-voltage relationship (I-V curve) of the whole cell hypotonic-sensitive current shifted from an isotonic I-V curve in a parallel way. Our results indicate that I(K1) and I(KATP) do not participate in membrane potential changes induced by hypotonic solution at least in the guinea pig ventricular myocytes with sufficient intracellular ATP.
Kocic
Ivan
I
Department of Cardiovascular Disease, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. ikocic@amedec.amg.gda.pl
Hirano
Yuji
Y
Hiraoka
Masayasu
M
D000818:Animals; D002839:Chromans / Q000494:pharmacology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D007038:Hypotonic Solutions; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D016276:Ventricular Function
D002839:Chromans; D007038:Hypotonic Solutions; D010880:Piperidines; D015221:Potassium Channels; C063899:terikalant; D005905:Glyburide