Pacemaker mechanism of porcine sino-atrial node cells.
In cardiac sino-atrial node (SAN) cells, time- and voltage-dependent changes in the gating of various ionic currents provide spontaneous, stable and repetitive firing of action potentials. To address the ionic nature of the species-dependent heart rate, action potentials and membrane currents were recorded in single cells dissociated from the porcine SAN, and compared with those from SAN cells of rabbits, guinea-pigs and mice. The porcine SAN cells exhibited spontaneous activity with a frequency of 60-80 min(-1), which was much slower than that of rabbit SAN cells. Under voltage clamp conditions, depolarization activated the L-type Ca2+ current (I(CaL)) followed by a gradual activation of the delayed rectifier K+ current (I(K)) while hyperpolarization activated the hyperpolarization-activated cation current (I(h)). It was found that the major component of I(K) in porcine SAN is the slowly activating I(K) (I(Ks)), in contrast to SAN cells of the rabbit and other species in which the rapid I(K) (I(Kr)) plays an active role in repolarization and the subsequent pacemaker depolarization. Replacement of rabbit I(Kr) with porcine I(Ks) and a slight modification in the gating parameters and amplitudes of other current systems in the 'Kyoto Model' gave an adequate reconstruction of spontaneous action potentials as well as of the voltage clamp recordings. We conclude that the density and the kinetics of I(K) contribute, in part, to the different heart rates of various species.
Ono
Kyoichi
K
Department of Pharmacology, Akita University School of Medicine, Hondoh 1-1-1, Akita 010-8543, Japan. onok@med.akita-u.ac.jp
Shibata
Shigehiro
S
Iijima
Toshihiko
T
D000200:Action Potentials; D000818:Animals; D001683:Biological Clocks; D003198:Computer Simulation; D051668:Delayed Rectifier Potassium Channels; D004553:Electric Conductivity; D008955:Models, Cardiovascular; D015221:Potassium Channels / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology*
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated