BACKGROUND: Recent experimental and clinical studies on atrial flutter have demonstrated that the crista terminalis (CT) plays an important role in the genesis of atrial reentry. To elucidate the underlying mechanism of its role, we characterized the electrophysiological repolarization properties of CT cells by comparing them with those of the pectinate muscles (PM). METHODS AND RESULTS: After action potential properties of both regions were compared by conventional microelectrode technique in multicellular atrial tissues, the whole-cell clamp experiments were applied in atrial cells isolated from both regions. Action potential duration (APD) was more prolonged in CT than in PM in multicellular preparations (APD90 77 +/- 5 ms versus 52 +/- 8 ms at 1 Hz, P < .01), though the other properties did not differ significantly. Similarly, in isolated atrial cells, APD was more prolonged in CT cells than in PM cells (APD90 63 +/- 7 ms versus 41 +/- 6 ms at 0.1 Hz, P < .01). Isolated single cells were larger in CT than in PM. The whole-cell clamp recordings showed no definite distinctions in the density of the voltage-dependent L-type Ca2+ current and the inwardly rectifying K+ current between these cells but revealed a significant reduction of the density of the 4-aminopyridine-sensitive transient outward current (Ito) in CT cells compared with that in PM cells (6.3 +/- 0.7 pA/pF versus 10.3 +/- 0.8 pA/pF at +20 mV, P < .05). However, no differences in the kinetics or the voltage dependence of Ito were observed between the cells. The time course of recovery from inactivation of Ito was also similar in both types of cells. CONCLUSIONS: These results suggest that the preferential reduction in the density of Ito in the CT cells could contribute to prolong their APD, which may be related to the genesis of atrial reentry.
BACKGROUND: Recent experimental and clinical studies on atrial flutter have demonstrated that the crista terminalis (CT) plays an important role in the genesis of atrial reentry. To elucidate the underlying mechanism of its role, we characterized the electrophysiological repolarization properties of CT cells by comparing them with those of the pectinate muscles (PM). METHODS AND RESULTS: After action potential properties of both regions were compared by conventional microelectrode technique in multicellular atrial tissues, the whole-cell clamp experiments were applied in atrial cells isolated from both regions. Action potential duration (APD) was more prolonged in CT than in PM in multicellular preparations (APD90 77 +/- 5 ms versus 52 +/- 8 ms at 1 Hz, P < .01), though the other properties did not differ significantly. Similarly, in isolated atrial cells, APD was more prolonged in CT cells than in PM cells (APD90 63 +/- 7 ms versus 41 +/- 6 ms at 0.1 Hz, P < .01). Isolated single cells were larger in CT than in PM. The whole-cell clamp recordings showed no definite distinctions in the density of the voltage-dependent L-type Ca2+ current and the inwardly rectifying K+ current between these cells but revealed a significant reduction of the density of the 4-aminopyridine-sensitive transient outward current (Ito) in CT cells compared with that in PM cells (6.3 +/- 0.7 pA/pF versus 10.3 +/- 0.8 pA/pF at +20 mV, P < .05). However, no differences in the kinetics or the voltage dependence of Ito were observed between the cells. The time course of recovery from inactivation of Ito was also similar in both types of cells. CONCLUSIONS: These results suggest that the preferential reduction in the density of Ito in the CT cells could contribute to prolong their APD, which may be related to the genesis of atrial reentry.
Authors: Alexey V Glukhov; Marina Balycheva; Jose L Sanchez-Alonso; Zeki Ilkan; Anita Alvarez-Laviada; Navneet Bhogal; Ivan Diakonov; Sophie Schobesberger; Markus B Sikkel; Anamika Bhargava; Giuseppe Faggian; Prakash P Punjabi; Steven R Houser; Julia Gorelik Journal: Circulation Date: 2015-10-08 Impact factor: 29.690