The role of Ca2+ release from sarcoplasmic reticulum in the regulation of sinoatrial node automaticity.
The role of Ca2+ release channels in the sarcoplasmic reticulum in modulating physiological automaticity of the sinoatrial (SA) node was studied by recording transmembrane action potentials and membrane ionic currents in small preparations of the rabbit SA node. Ryanodine, which modifies the conductance and gating behavior of the Ca2+ release channels, was used to block Ca2+ release from the sarcoplasmic reticulum. Superfusion of 1-mM ryanodine decreased the spontaneous firing frequency as well as the maximal rate of depolarization of the SA, and these reductions reached a steady state within approximately 5 min. The action potential recordings revealed that the latter part of diastolic depolarization was depressed and that the take-off potential became less negative. This suggested that the negative chronotropic effect of ryanodine resulted from the blockade of physiological Ca2+ release from the sarcoplasmic reticulum. In voltage clamp experiments, using double-microelectrode techniques, ryanodine did not markedly reduce the Ca2+ current (ICa) but decreased the delayed rectifying K+ current (IK), the steady-state inward current (Iss), and the hyperpolarization-activated inward current (Ih). These observations suggest that, even when the function of C2+ channels in the cell membrane is normally maintained, depression of Ca2+ release channels in the sarcoplasmic reticulum would prevent sufficient elevation of the Ca2+ concentration in SA node cells for the activation of various ionic currents, and, thus adversely affect the physiological automaticity of this primary cardiac pacemaker.
Hata
T
T
Cardiovascular Institute, Fujita Health University School of Medicine, Aichi, Japan.
Noda
T
T
Nishimura
M
M
Watanabe
Y
Y
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D012433:Ryanodine / Q000378:metabolism / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012849:Sinoatrial Node / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*
D015221:Potassium Channels; D012433:Ryanodine; D002118:Calcium