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Differential effects of MS-551 and E-4031 on action potentials and the delayed rectifier K+ current in rabbit ventricular myocytes.
Cardiovasc Res. 1996 Jun; 31(6):963-74.CR

Abstract

OBJECTIVE

The frequency-dependent effects of MS-551 on the action potential duration (APD) and the underlying ionic mechanisms were investigated in comparison with those of E-4031.

METHODS

Whole-cell clamp techniques were used to study action potentials and ionic currents in enzymatically isolated rabbit ventricular myocytes.

RESULTS

The frequency-response obtained within the range of 0.1 to 3.3 Hz was different for MS-551 and E-4031. The APD prolongation by MS-551 (10 microM) was significant at 0.5-3.3 Hz, whereas that by E-4031 (1 microM) was significant at 0.1-1.0 Hz. The prolongation by MS-551 (10 microM) of APD of a test action potential, which was preceded by a train of 1.0 Hz stimulation, decreased progressively as the rest duration increased, whereas that by E-4031 (1 microM) remained at the same level. Both MS-551 (10 microM) and E-4031 (1 microM) significantly decreased IK, but showed no effects on the transient outward current (Ito) and the inward rectifier K+ current (IKl). The development of the block on IK and the recovery from the block by MS-551 were voltage dependent. At a holding potential of -50 mV, MS-551 reduced the tail current to a similar extent (21-34%, n = 6) across all the tested durations of the depolarizing pulses to +10 mV, whereas at -75 mV, the intensity of the block progressively increased as the durations of depolarizing pulses were prolonged. The recovery from the block by MS-551 was absent at -50 mV, but occurred at -75 mV with a time constant of 577 +/- 179 ms (n = 6). The development of the block on IK by E-4031 was voltage and time independent. No recovery from the block was observed for E-4031 at either -50 or -75 mV.

CONCLUSIONS

These findings suggest that MS-551 produces frequency-dependent class III action, presumably due to the voltage-dependent binding and unbinding to the IK channels. The reverse frequency dependence of class III action by E-4031 cannot be explained by the effects on IK.

Authors+Show Affiliations

Department of Circulation, Nagoya University, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

8759253

Citation

Cheng, J, et al. "Differential Effects of MS-551 and E-4031 On Action Potentials and the Delayed Rectifier K+ Current in Rabbit Ventricular Myocytes." Cardiovascular Research, vol. 31, no. 6, 1996, pp. 963-74.
Cheng J, Kamiya K, Kodama I, et al. Differential effects of MS-551 and E-4031 on action potentials and the delayed rectifier K+ current in rabbit ventricular myocytes. Cardiovasc Res. 1996;31(6):963-74.
Cheng, J., Kamiya, K., Kodama, I., & Toyama, J. (1996). Differential effects of MS-551 and E-4031 on action potentials and the delayed rectifier K+ current in rabbit ventricular myocytes. Cardiovascular Research, 31(6), 963-74.
Cheng J, et al. Differential Effects of MS-551 and E-4031 On Action Potentials and the Delayed Rectifier K+ Current in Rabbit Ventricular Myocytes. Cardiovasc Res. 1996;31(6):963-74. PubMed PMID: 8759253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of MS-551 and E-4031 on action potentials and the delayed rectifier K+ current in rabbit ventricular myocytes. AU - Cheng,J, AU - Kamiya,K, AU - Kodama,I, AU - Toyama,J, PY - 1996/6/1/pubmed PY - 1996/6/1/medline PY - 1996/6/1/entrez SP - 963 EP - 74 JF - Cardiovascular research JO - Cardiovasc Res VL - 31 IS - 6 N2 - OBJECTIVE: The frequency-dependent effects of MS-551 on the action potential duration (APD) and the underlying ionic mechanisms were investigated in comparison with those of E-4031. METHODS: Whole-cell clamp techniques were used to study action potentials and ionic currents in enzymatically isolated rabbit ventricular myocytes. RESULTS: The frequency-response obtained within the range of 0.1 to 3.3 Hz was different for MS-551 and E-4031. The APD prolongation by MS-551 (10 microM) was significant at 0.5-3.3 Hz, whereas that by E-4031 (1 microM) was significant at 0.1-1.0 Hz. The prolongation by MS-551 (10 microM) of APD of a test action potential, which was preceded by a train of 1.0 Hz stimulation, decreased progressively as the rest duration increased, whereas that by E-4031 (1 microM) remained at the same level. Both MS-551 (10 microM) and E-4031 (1 microM) significantly decreased IK, but showed no effects on the transient outward current (Ito) and the inward rectifier K+ current (IKl). The development of the block on IK and the recovery from the block by MS-551 were voltage dependent. At a holding potential of -50 mV, MS-551 reduced the tail current to a similar extent (21-34%, n = 6) across all the tested durations of the depolarizing pulses to +10 mV, whereas at -75 mV, the intensity of the block progressively increased as the durations of depolarizing pulses were prolonged. The recovery from the block by MS-551 was absent at -50 mV, but occurred at -75 mV with a time constant of 577 +/- 179 ms (n = 6). The development of the block on IK by E-4031 was voltage and time independent. No recovery from the block was observed for E-4031 at either -50 or -75 mV. CONCLUSIONS: These findings suggest that MS-551 produces frequency-dependent class III action, presumably due to the voltage-dependent binding and unbinding to the IK channels. The reverse frequency dependence of class III action by E-4031 cannot be explained by the effects on IK. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/8759253/Differential_effects_of_MS_551_and_E_4031_on_action_potentials_and_the_delayed_rectifier_K+_current_in_rabbit_ventricular_myocytes_ DB - PRIME DP - Unbound Medicine ER -