摘要
Background Atrial fibrillation (AF) is the most common supraventriculararrhythmia in clinical practice. Chronic atrial fibrillation (CAF) is associated with ionicremodeling. However, little is known about the activity of ATP-sensitive potassium current I_(K,ATP) during CAF. So we studied the changes of I_(K, ATP) density and allosteric modulation ofATP-sensitivity by intracellular pH during CAF. Methods Myocardium samples were obtained from theright auricular appendage of patients with rheumatic heart disease complicated with valvular diseasein sinus rhythm (SR) or CAF. There were 14 patients in SR group and 9 patients in CAF group. Singleatrial cells were isolated using an enzyme dispersion technique. IKiATP was recorded using thewhole-cell and inside-out configuration of voltage-clamp techniques. In whole-cell model, myocytesof SR and CAF groups were perfused with simulated ischemic solution to elicit I_(K, ATP). Ininside-out configuration, the internal patch membranes were exposed to different ATP concentrationsin pH 7. 4 and 6. 8. Results Under simulated ischemia, I_(K, ATP) current density of CAF group wassignificantly higher than in SR group [(83.5 ± 10.8) vs. (58.7 ±8.4) pA/pF, P < 0. 01 ] . I_(K,ATP) of the two groups showed ATP concentration-dependent inhibition. The ATP concentration for 50%current inhibition (IC_(50) ) for the SR group was significantly different in pH 7. 4 and pH 6. 8(24 vs. 74 μmol/L, P < 0. 01). The IC_(50) did not change significantly in CAF group when the pHdecreased from 7. 4 to 6. 8. Conclusions During CAF, I_(K, ATP) current density was increased andits allosteric modulation of ATP-sensitivity by intracellular pH was diminished.
Background Atrial fibrillation (AF) is the most common supraventriculararrhythmia in clinical practice. Chronic atrial fibrillation (CAF) is associated with ionicremodeling. However, little is known about the activity of ATP-sensitive potassium current I_(K,ATP) during CAF. So we studied the changes of I_(K, ATP) density and allosteric modulation ofATP-sensitivity by intracellular pH during CAF. Methods Myocardium samples were obtained from theright auricular appendage of patients with rheumatic heart disease complicated with valvular diseasein sinus rhythm (SR) or CAF. There were 14 patients in SR group and 9 patients in CAF group. Singleatrial cells were isolated using an enzyme dispersion technique. IKiATP was recorded using thewhole-cell and inside-out configuration of voltage-clamp techniques. In whole-cell model, myocytesof SR and CAF groups were perfused with simulated ischemic solution to elicit I_(K, ATP). Ininside-out configuration, the internal patch membranes were exposed to different ATP concentrationsin pH 7. 4 and 6. 8. Results Under simulated ischemia, I_(K, ATP) current density of CAF group wassignificantly higher than in SR group [(83.5 ± 10.8) vs. (58.7 ±8.4) pA/pF, P < 0. 01 ] . I_(K,ATP) of the two groups showed ATP concentration-dependent inhibition. The ATP concentration for 50%current inhibition (IC_(50) ) for the SR group was significantly different in pH 7. 4 and pH 6. 8(24 vs. 74 μmol/L, P < 0. 01). The IC_(50) did not change significantly in CAF group when the pHdecreased from 7. 4 to 6. 8. Conclusions During CAF, I_(K, ATP) current density was increased andits allosteric modulation of ATP-sensitivity by intracellular pH was diminished.
