Rate-dependent prolongation of action potential duration in isolated rat ventricular myocytes.
Rate-dependent alterations of action potential duration (APD) in rat ventricular myocytes were investigated. Action potentials of the isolated myocytes were recorded with patch electrodes containing EGTA (11 mM), and showed a marked rate-dependent prolongation in the APD (0.2-5 Hz). This prolongation was significantly inhibited in the presence of 4-aminopyridine (4-AP), a blocker of the transient outward K+ current (Ito). Thus, the rate-dependent decrease in Ito may underlie the change in APD. In contrast, the action potentials recorded from rat ventricular papillary muscles with conventional microelectrodes did not show rate-dependent alterations in the APD, i.e., the APD remained practically unaltered at the frequency range of 0.2-5 Hz. These results suggest that the rate-dependent prolongation of APD (due to rate-dependent blockade of Ito) becomes evident when the intracellular Ca2+ was chelated by the internal application of EGTA via patch pipette. We speculate that the rate-dependent prolongation of APD (via decreases in Ito) is masked in the ventricular papillary muscles, probably due to rate-dependent decreases in the inward current (e.g., electrogenic Na(+)-Ca2+ exchange current) that is regulated by the intracellular calcium.
Shigematsu
S
S
Oita Medical University, Japan.
Kiyosue
T
T
Sato
T
T
Arita
M
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D010210:Papillary Muscles / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
D002614:Chelating Agents; D004533:Egtazic Acid; D015761:4-Aminopyridine; D002118:Calcium