Changes of I_(K,ATP) current density and allosteric modulation during chronic atrial fibrillation

来源 :Chinese Medical Journal | 被引量 : 0次 | 上传用户:jason008_xu
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Background Atrial fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. Chronic atrial fibrillation (CAF) is associated with ionic remodeling. 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 of ATP-sensitivity by intracellular pH during CAF.Methods Myocardium samples were obtained from the right auricular appendage of patients with rheumatic heart disease complicated with valvular disease in sinus rhythm (SR) or CAF. There were 14 patients in SR group and 9 patients in CAF group. Single atrial cells were isolated using an enzyme dispersion technique. I_(K,ATP) was recorded using the whole-cell and inside-out configuration of voltage-clamp techniques. In whole-cell model, myocytes of SR and CAF groups were perfused with simulated ischemic solution to elicit I_(K,ATP). In inside-out configuration, the internal patch membranes were exposed to different ATP concentrations in pH 7.4 and 6.8.Results Under simulated ischemia, I_(K,ATP) current density of CAF group was significantly 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 pH decreased from 7.4 to 6.8.Conclusions During CAF, I_(K,ATP) current density was increased and its allosteric modulation of ATP-sensitivity by intracellular pH was diminished. Background Atrial fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. Chronic atrial fibrillation (CAF) is associated with ionic remodeling. 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 of ATP-sensitivity by intracellular pH during CAF. Myocardium samples were obtained from the right auricular appendage of patients with rheumatic heart disease complicated with valvular disease in sinus rhythm (SR) or CAF. There were 14 patients in SR group and 9 patients in CAF group. Single atrial cells were isolated using an enzyme dispersion technique. I_ (K, ATP) was recorded using the whole-cell and inside-out configuration of voltage-clamp techniques. In whole-cell model, myocytes of SR and CAF groups were perfused with simulated ischemic solution to elicit I_ (K, ATP). In inside-out configuration, the internal patch membranes wer (K, ATP) current density of CAF group was significantly higher than in SR group [(83.5 ± 10.8) vs. (58.7 ± 8.4) pA / The ATP concentration for 50% current inhibition (IC 50 (50) for the two groups showed significant differences 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 pH decreased from 7.4 to 6.8. and its allosteric modulation of ATP-sensitivity by intracellular pH was diminished.
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