title: Calcium transient and sodium-calcium exchange current in human versus rabbit sinoatrial node pacemaker cells.
abstract: There is an ongoing debate on the mechanism underlying the pacemaker activity of sinoatrial node (SAN) cells, focusing on the relative importance of the "membrane clock" and the "Ca(2+) clock" in the generation of the small net membrane current that depolarizes the cell towards the action potential threshold. Specifically, the debate centers around the question whether the membrane clock-driven hyperpolarization-activated current, I f , which is also known as the "funny current" or "pacemaker current," or the Ca(2+) clock-driven sodium-calcium exchange current, I NaCa, is the main contributor to diastolic depolarization. In our contribution to this journal's "Special Issue on Cardiac Electrophysiology," we present a numerical reconstruction of I f and I NaCa in isolated rabbit and human SAN pacemaker cells based on experimental data on action potentials, I f , and intracellular calcium concentration ([Ca(2+)] i ) that we have acquired from these cells. The human SAN pacemaker cells have a smaller I f , a weaker [Ca(2+)] i transient, and a smaller I NaCa than the rabbit cells. However, when compared to the diastolic net membrane current, I NaCa is of similar size in human and rabbit SAN pacemaker cells, whereas I f is smaller in human than in rabbit cells.
authors.affiliation: Department of Anatomy, Embryology and Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, Amsterdam, The Netherlands.
authors.forename: Arie O
authors.initials: AO
authors.lastname: Verkerk
authors.forename: Marcel M G J
authors.initials: MM
authors.lastname: van Borren
authors.forename: Ronald
authors.initials: R
authors.lastname: Wilders
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D003198:Computer Simulation; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology*; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D013045:Species Specificity
chemical_list: D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium