Changes of IK, ATP current density and allosteric modulation during chronic atrial fibrillation.
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 (IK, ATP) during CAF. So we studied the changes of IK, 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. IK, 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 IK, 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, IK, 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]. IK, ATP of the two groups showed ATP concentration-dependent inhibition. The ATP concentration for 50% current inhibition (IC50) for the SR group was significantly different in pH 7.4 and pH 6.8 (24 vs. 74 micromol/L, P < 0.01). The IC50 did not change significantly in CAF group when the pH decreased from 7.4 to 6.8.


CONCLUSIONS
During CAF, IK, ATP current density was increased and its allosteric modulation of ATP-sensitivity by intracellular pH was diminished.
Wu
Gang
G
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Huang
Cong-xin
CX
Tang
Yan-hong
YH
Jiang
Hong
H
Wan
Jun
J
Chen
Hui
H
Xie
Qiang
Q
Huang
Zheng-rong
ZR
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000328:Adult; D000494:Allosteric Regulation; D001281:Atrial Fibrillation / Q000378:metabolism*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D015221:Potassium Channels / Q000502:physiology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate