Mexiletine-induced shortening of the action potential duration of ventricular muscles by activation of ATP-sensitive K+ channels.
A class Ib antiarrhythmic drug, mexiletine (100 microM) significantly shortened the action potential duration (APD) of guinea-pig ventricular muscles and this effect was completely abolished in the presence of glibenclamide (50 microM), a blocker of the ATP-sensitive K+ channel (KATP). Mexiletine significantly increased the open probability of uridine diphosphate-primed KATP channels, recorded in inside-out patches of the ventricular cells. The results suggest that mexiletine shortens the APD of ventricular muscles, at least in part, via activation of KATP.
Sato
T
T
Department of Physiology, Oita Medical University School of Medicine, Japan.
Shigematsu
S
S
Arita
M
M
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008801:Mexiletine / Q000494:pharmacology*; D008839:Microelectrodes; D010210:Papillary Muscles / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D014530:Uridine Diphosphate / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D008801:Mexiletine; D014530:Uridine Diphosphate; D000255:Adenosine Triphosphate; D005905:Glyburide