Prog Biophys Mol Biol 2021 Jun 18. Epub 2021 Jun 18.
Department of Medical Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, the Netherlands; Department of Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, Amsterdam, the Netherlands.
Background: Despite the many studies carried out over the past 40 years, the contribution of the HCN4 encoded hyperpolarization-activated 'funny' current (I) to pacemaker activity in the mammalian sinoatrial node (SAN), and the human SAN in particular, is still controversial and not fully established.
Objective: To study the contribution of I to diastolic depolarization of human SAN cells and its dependence on heart rate, cAMP levels, and atrial load.
Methods: HCN4 channels were expressed in human cardiac myocyte progenitor cells (CMPCs) and HCN4 currents assessed using perforated patch-clamp in traditional voltage clamp mode and during action potential clamp with human SAN-like action potential waveforms with 500-1500 ms cycle length, in absence or presence of forskolin to mimic β-adrenergic stimulation and a -15 mV command potential offset to mimic atrial load. Read More