Atrial fibrillation in the goat induces changes in monophasic action potential and mRNA expression of ion channels involved in repolarization

Introduction: Sustained atrial fibrillation (AF) is characterized by a mark ed shortening of the atrial effective refractory period (AERP) and a decrea se or reversal of its physiologic adaptation to heart rate. The aim of the present study was to investigate whether the AF-induced changes in AERP in the goat are associated with changes in the atrial monophasic action potent ial (MAP) and whether an abnormal expression of specific ion channels under lies such changes. Methods and Results: Following thoracotomy, MAPs were recorded from the fre e wail of the right atrium both before induction of AF (control) and after cardioversion of sustained AF (>2 months) in chronically instrumented goats . In control goats, MAP duration at 80% repolarization (MAPD(80)) shortened (P < 0.01) from 132 +/- 4 msec during slow pacing (400-msec interval) to 8 6 +/- 10 msec during fast pacing (180 msec), After cardioversion of sustain ed AF, the MAPD(80) during slow pacing was as short as 67 +/- 5 msec (elect rical remodeling). Increasing the pacing rate resulted in prolongation (P = 0.02) of the MAPD(80) to 91 +/- 6 msec. Also, MAPD(20) (20% repolarization ) shortened (P = 0.05) from 32 +/- 4 msec (400 msec) to 14 +/- 7 msec (180 msec) in the control goats, whereas it prolonged (P = 0.03) from 20 +/- 3 m sec (400 msec) to 33 +/- 5 msec (180 msec) in sustained AF. mRNA expression of the L-type Ca2+ channel <alpha>1c gene and Kv1.5 potassium channel gene , which underlie I-Ca and I-Kur, respectively, was reduced in sustained AF compared with sinus rhythm by 32% (P = 0.01) and 45% (P < 0.01), respective ly. No significant changes were found in the mRNA levels of the rapid Na+ c hannel, the Na+/Ca2+ exchanger, or the Kv4.2/4.3 channels responsible for I -to. Conclusion: AF-induced electrical remodeling in the goat comprises shorteni ng of MAPD and reversal of its physiologic rate adaptation. Changes in the time course of repolarization of the action potential are associated with c hanges in mRNA expression of the cy subunit genes of the L-type Ca2+ channe l and the Kv1.5 potassium channel.