Mechanisms for depolarization by l-palmitoylcarnitine in single guinea pig ventricular myocytes.
BACKGROUND
The changes of the resting potential (RP) and of the current-voltage (I-V) relationship induced by l-palmitoylcarnitine (l-PC) in the presence of the IKI blocker, cesium, or in the presence of the INa/K blocker, ouabain, were tested in guinea pig ventricular myocytes to ascertain the relative contributions of IKI and INa/K suppression to the membrane depolarization caused by this amphiphile.


RESULTS
Ramp voltages were applied to myocytes with the whole cell, patch clamp technique. l-PC (10 microM) produced additional membrane depolarization in the presence of either 10 mM Cs+ or 30 microM ouabain. In the presence of Cs+, l-PC, like 3 microM ouabain, shifted current inward at potentials negative to -20 mV as a result of INa/K blockade. In the presence of 30 microM ouabain, l-PC, like Cs+, shifted current inward at potentials between -27 and -88 mV and outward at potentials negative to -88 mV. This is attributed to IKI block because the current was inwardly rectifying, with a reversal potential near EK. When l-PC or ouabain inhibited INa/K, the presence of an Ni(2+)-sensitive component attributed to INa/Ca distorted the membrane I-V relationship, particularly in the presence of Cs+. The relative contributions of IKI and INa/K block by l-PC were voltage dependent. At the RP, l-PC produced a greater block of INa/K than of IKI.


CONCLUSIONS
l-PC depolarizes the resting membrane by inhibiting both IKI and INa/K. It is concluded that suppression of INa/K by l-PC predominates over block of IKI to depolarize the membrane at the RP.
Shen
J B
JB
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030, USA.
Pappano
A J
AJ
D000818:Animals; D002586:Cesium / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D009532:Nickel / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D010172:Palmitoylcarnitine; D002586:Cesium; D010042:Ouabain; D009532:Nickel; D000254:Sodium-Potassium-Exchanging ATPase