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Inhibition of Na+-K+ pump and L-type Ca2+ channel by glibenclamide in Guinea pig ventricular myocytes.
J Pharmacol Exp Ther. 2005 Jan; 312(1):61-8.JP

Abstract

Glibenclamide, a potent cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel blocker, is frequently used to study function and regulation of CFTR Cl(-) channels. In this study, the effects of glibenclamide on intracellular Na(+) concentration ([Na(+)](i)), contraction, Ca(2+) transient, and membrane potential were investigated in isolated guinea pig ventricular myocytes. Glibenclamide increased [Na(+)](i) and decreased contraction and Ca(2+) transient. However, glibenclamide did not change membrane potential. To determine whether inhibition of Na(+)-K(+) pumps and L-type Ca(2+) channels is responsible for the increase of [Na(+)](i) and the decrease of contraction, we tested the effects of glibenclamide on Na(+)-K(+) pump current and L-type Ca(2+) current (I(Ca,L)). Glibenclamide decreased Na(+)-K(+) pump current and I(Ca,L) in a concentration-dependent manner. In the presence of Cl(-) channel inhibitors, glibenclamide depolarized diastolic membrane potential and reduced action potential duration. This result suggests that the reason for lack of effect of glibenclamide on membrane potential might be due to its combined inhibitory effects on the Na(+)-K(+) pump, the L-type Ca(2+) channel, and Cl(-) channels, which may have opposing effects on membrane potential. These results indicate that glibenclamide increases [Na(+)(i)] by inhibiting the Na(+)-K(+) pump and decreases contraction and Ca(2+) transient, in addition, by blocking the L-type Ca(2+) channel.

Authors+Show Affiliations

Lee SY
Department of Life Science, Pohang University of Science and Technology, Pohang, Kyung-buk, 790-784, Republic of Korea.
Lee CO
No affiliation info available

MeSH

AnimalsCalciumCalcium Channels, L-TypeCells, CulturedChloride ChannelsCystic Fibrosis Transmembrane Conductance RegulatorGlyburideGuinea PigsHeart VentriclesHypoglycemic AgentsMembrane PotentialsMyocytes, CardiacSodiumSodium-Potassium-Exchanging ATPase

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15365090

Citation

Lee, So-Young, and Chin O. Lee. "Inhibition of Na+-K+ Pump and L-type Ca2+ Channel By Glibenclamide in Guinea Pig Ventricular Myocytes." The Journal of Pharmacology and Experimental Therapeutics, vol. 312, no. 1, 2005, pp. 61-8.
Lee SY, Lee CO. Inhibition of Na+-K+ pump and L-type Ca2+ channel by glibenclamide in Guinea pig ventricular myocytes. J Pharmacol Exp Ther. 2005;312(1):61-8.
Lee, S. Y., & Lee, C. O. (2005). Inhibition of Na+-K+ pump and L-type Ca2+ channel by glibenclamide in Guinea pig ventricular myocytes. The Journal of Pharmacology and Experimental Therapeutics, 312(1), 61-8.
Lee SY, Lee CO. Inhibition of Na+-K+ Pump and L-type Ca2+ Channel By Glibenclamide in Guinea Pig Ventricular Myocytes. J Pharmacol Exp Ther. 2005;312(1):61-8. PubMed PMID: 15365090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of Na+-K+ pump and L-type Ca2+ channel by glibenclamide in Guinea pig ventricular myocytes. AU - Lee,So-Young, AU - Lee,Chin O, Y1 - 2004/09/13/ PY - 2004/9/15/pubmed PY - 2005/4/14/medline PY - 2004/9/15/entrez SP - 61 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 312 IS - 1 N2 - Glibenclamide, a potent cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel blocker, is frequently used to study function and regulation of CFTR Cl(-) channels. In this study, the effects of glibenclamide on intracellular Na(+) concentration ([Na(+)](i)), contraction, Ca(2+) transient, and membrane potential were investigated in isolated guinea pig ventricular myocytes. Glibenclamide increased [Na(+)](i) and decreased contraction and Ca(2+) transient. However, glibenclamide did not change membrane potential. To determine whether inhibition of Na(+)-K(+) pumps and L-type Ca(2+) channels is responsible for the increase of [Na(+)](i) and the decrease of contraction, we tested the effects of glibenclamide on Na(+)-K(+) pump current and L-type Ca(2+) current (I(Ca,L)). Glibenclamide decreased Na(+)-K(+) pump current and I(Ca,L) in a concentration-dependent manner. In the presence of Cl(-) channel inhibitors, glibenclamide depolarized diastolic membrane potential and reduced action potential duration. This result suggests that the reason for lack of effect of glibenclamide on membrane potential might be due to its combined inhibitory effects on the Na(+)-K(+) pump, the L-type Ca(2+) channel, and Cl(-) channels, which may have opposing effects on membrane potential. These results indicate that glibenclamide increases [Na(+)(i)] by inhibiting the Na(+)-K(+) pump and decreases contraction and Ca(2+) transient, in addition, by blocking the L-type Ca(2+) channel. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15365090/Inhibition_of_Na+_K+_pump_and_L_type_Ca2+_channel_by_glibenclamide_in_Guinea_pig_ventricular_myocytes_ DB - PRIME DP - Unbound Medicine ER -