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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.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Cheng, Jian-Hua Kamiya, Kaichiro Kodama, Itsuo Toyama, Junji |
| Copyright Year | 1996 |
| 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/S0008-6363(96)00049-1 |
| Alternate Webpage(s) | http://cardiovascres.oxfordjournals.org/content/cardiovascres/31/6/963.full.pdf |
| Alternate Webpage(s) | https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cardiovascres/31/6/10.1016/S0008-6363(96)00049-1/2/31-6-963.pdf?Expires=1493029849&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=W6NFpl9PJFClJ5RcKAnZTEbzcVmAKO5e6jt2nsnWq8R5c8lDppMekBomNlTH5Hciq6kpEsGo4sXo7khP1Iqv5e2D8TvNW2-JCG0YPzHJJLkg2EFfgRnfonYIDO5atLYvYh6ciuAz5YWPE2ZgvY2avyjqh83W4jg6ZsMvhmlHvxid~k6GllJVo6R50Lctoq-7nc4Ftz5XxJopH8UcRDSG2C5OP0~DM7IYT10i6Xx3Ja15Y5IyzMg84akudEyKYM2IaXHsNOTCiHHIrCp1SzqlOYYTQ76QIrCF7zwwbng5OTgO32Ztcw5gjTTR3X43TR5BHghhCQY5jFWeKVCju1oRlA__ |
| Alternate Webpage(s) | https://watermark.silverchair.com/31-6-963.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAcEwggG9BgkqhkiG9w0BBwagggGuMIIBqgIBADCCAaMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMLzWh1lNU94Rnlbk3AgEQgIIBdFYwMY1LQDiN-dxFNpGDh3TYQ6DP0eMNDGbAq_GNcZuRqrXQXeKHom486yw_wqekHsf2_TupwurQAjw8iXv5KZqiXznBVEuJGJRzomnVMAn_GguDeH8SJglAjG0KWkCQND0HE0CFdYdwtvwnJ42UHMTDxAo9Ps2lPH_a5Y19g5bMINwls-Nnfl65mrbDlo7EkwWcAlQDLEo0laforBDsAbR3SaYjtRj7V6Yk8TkQZUfaNXm8UAUsE3mBM0YJTYlhC35nRR_8zh8y1ukkuE08Z947JY5vlpEN21uo_1dqtPlXJABiP9d79IZ0Gv15dNCkdTrkyJejqmuK8YxSPnCklm-_A6Hu9LBw3P7LqtkMtKwz1eAorl0shyno3ZVCsAGokSXSLmuDzHqGx-mCr8jE5Tu_xNm_5o6RtxsLlJ764JcgHFu5Ukf5tAyxqV37f9O8hlVFUEzr081v90Lkpw2uGTLyfbg7UxF7tsO1o9rTJ6K8cSxnTg |
| PubMed reference number | 8759253 |
| Alternate Webpage(s) | https://doi.org/10.1016/S0008-6363%2896%2900049-1 |
| Journal | Medline |
| Volume Number | 31 |
| Issue Number | 6 |
| Journal | Cardiovascular research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
