Effect of neurotrophin p75 receptor activation on transmural repolarization dispersion of outward potassium current in rabbits with myocardial infarction

AIM: To elucidate the effect of neurotrophin p75 receptor (p75NTR) on the transmural repolarization dispersion of the transient outward potassium current (Ito,f) of three layers of left ventricular myocytes in rabbits with myocardial infarction (MI). METHODS: Forty Japanese rabbits were divided into four groups: 1) HMI group, 2) p75 NTR activation group, 3) p75 NTR inhibition group and 4) sham group. Cardiomyocytes were isolated with enzyme digestion and the currents were recorded by whole-cell patch-clamp technique. RESULTS: Compared with those in the sham group, the densities of Ito,f in the HMI group and p75NTR(+) group were significantly reduced (P<0.01, n=10), especially in midmyocytes. This difference was reduced by inhibitor of p75NTR. Current densities of Ito,f in p75NTR(-) group was similar to that in sham group. Compared with that in sham group, the steady-state inactivation curve of Ito,f in the midmyocytes shifted to the negative in p75NTR(+) and HMI groups, and no obvious changes were observed in p75NTR(-) group. Significant differences were observed in the time constant values of closed-state inactivation of Ito,f in three layers of myocytes among the four groups, and closed-state inactivation was faster in p75NTR(+) and HMI groups, especially in p75NTR(+) group. The time constant values of closed-state inactivation of Ito,f in p75NTR(-) group was similar to that in sham group. CONCLUSIONS: Activation of p75NTR(+) reduces the current densities of Ito,f of three layers of myocytes, especially those in midmyocytes, which may result in the increase of transmural repolarization dispersion and incidence of arrhythmia.