Abstract
The block of the transient outward K+ current (Ito) by disopyramide was studied in isolated rat right ventricular myocytes using whole cell patch-clamp techniques. Disopyramide at a concentration of 10 to 1000 μM reduced peak Ito and accelerated the apparent rate of current inactivation. The onset of block was assessed using a double pulse protocol with steps from −70 to +50 mV. As the duration of the first (conditioning) pulse was increased from 1 to 50 ms, block was increased. Further prolongation of the conditioning pulse resulted in relief of block, which was nearly complete with a 1-s conditioning pulse. In the absence of drug, the recovery from inactivation of Ito at −70 mV was fast and best fit with a single exponential function having a time constant of 33 ± 13 ms. In contrast, in the presence of 100 μM disopyramide, recovery from apparent inactivation was biexponential with time constants of 35 ± 13 ms and 7.16 ± 1.5 s. The time course of the slow component was used to estimate recovery of channels from block by disopyramide. Recovery from block was voltage-dependent, suggesting that disopyramide was trapped by the open channel. Taken together, these results suggest that disopyramide rapidly blocks channels in the open state and that unblock occurs from the inactivated state.
Footnotes
-
Send reprint requests to: Dr. Jose A. Sanchez-Chapula, CUIB, Universidad de Colima, Apdo. Postal 199, C.P. 28000, Colima, Col. Mexico. E-mail: sancheza{at}cgic.ucol.mx
-
1 This study was supported by Consejo Nacional de Ciencia y Tecnologia (Mexico) Grant 3729P-M.
- Abbreviations:
- Ito
- transient outward K+ current
- IK
- delayed rectifying outward K+ current
- Isus
- sustained current
- 4-AP
- 4-aminopyridine
- HP
- holding potential
- Received January 21, 1999.
- Accepted April 19, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|