Fig. 6.

HCN4 channels in HEK cells pass a biphasic current with limited voltage-dependent gating in response to sinoatrial APs. (A) Representative ivabradine-sensitive HCN4 current in the absence of cAMP (gray) recorded from a HEK cell in response to APs recorded from a SAM in 1 nM isoproterenol (Top). (B) Representative ivabradine-sensitive HCN4 current with 1 mM cAMP in the intracellular solution (pink) recorded in a HEK cell in response to APs recorded from a SAM in 1 µM isoproterenol (Top). Horizontal lines indicate zero voltage or zero current levels. (C) Representative current–voltage relationships of ivabradine-sensitive HCN4 currents in control (gray) or 1 mM cAMP (pink). Black arrows indicate the progression of the current–voltage relationship over time. (C, Inset) Average current–voltage relationships of ivabradine-sensitive HCN4 currents in control (black) and 1 mM cAMP (red). (D) Average (± SEM) HCN4 current amplitude recorded at −60 mV during the latter diastolic depolarization (DD; circles) and AP repolarization (Repol; diamonds) in control (black) and 1 mM cAMP (red). Individual recordings in control (gray) or 1 mM cAMP (pink) are shown using smaller symbols. Number of replicates and details of statistical tests can be found in SI Appendix, Table S4.