Fig. 6

Tmem161b heterozygosity disrupts wild-type electrophysiology by increasing Ca²⁺ and K⁺ current densities in cardiomyocytes. (A) Cell isolation approach used for patch-clamp experiments depicted in B–I. (B) Representative APs from patch-clamping of adult cardiomyocytes isolated from adult wild-type and tmem161b^+/− fish. Inset shows first derivative of the AP upstroke and the arrow indicates maximal upstroke velocity (dV/dtmax). (C) Average APDs showing a decrease in APD at 20% repolarization (APD20), but an increase in APD at 50 and 90% repolarization (APD50 and APD90, respectively) in tmem161b^+/− cells (pacing at 1 Hz; mean ± SEM, n = 8, *P < 0.05). (D) Prolonged AP durations are most prominent at low-pacing frequencies. (E) Example of APs paced at 0.2 Hz showing EADs in wild-type versus tmem161b^+/− cells. (F) Incidence of EADs is significantly higher in tmem161b^+/− cells. (G, Top) Voltage-clamp protocol used to measure the inward rectifier K⁺ current (I_K1), the L-type Ca²⁺ current, and the rapid component of the delayed rectifier K⁺ current (I_Kr). (Bottom) Typical net membrane currents at −100 mV (I_K1), 0 mV (ICa,L), and +40 mV (I_Kr). (H) Average current-voltage (I-V) relationships of I_K1 and I_Kr showing no effect on I_K1, but an increase in I_Kr density in tmem161b^+/− cells. (I) Average I-V relationships of ICa,L showing an increase in inwardly directed current in tmem161b^+/− cells.