Sarcoplasmic reticulum Ca2+ release is not a dominating factor in sinoatrial node pacemaker activity.
Recent work on isolated sinoatrial node cells from rabbit has suggested that sarcoplasmic reticulum Ca2+ release plays a dominant role in the pacemaker potential, and ryanodine at a high concentration (30 micromol/L blocks sarcoplasmic reticulum Ca2+ release) abolishes pacemaking and at a lower concentration abolishes the chronotropic effect of beta-adrenergic stimulation. The aim of the present study was to test this hypothesis in the intact sinoatrial node of the rabbit. Spontaneous activity and the pattern of activation were recorded using a grid of 120 pairs of extracellular electrodes. Ryanodine 30 micromol/L did not abolish spontaneous activity or shift the position of the leading pacemaker site, although it slowed the spontaneous rate by 18.9+/-2.5% (n=6). After ryanodine treatment, beta-adrenergic stimulation still resulted in a substantial chronotropic effect (0.3 micromol/L isoproterenol increased spontaneous rate by 52.6+/-10.5%, n=5). In isolated sinoatrial node cells from rabbit, 30 micromol/L ryanodine slowed spontaneous rate by 21.5+/-2.6% (n=13). It is concluded that sarcoplasmic reticulum Ca2+ release does not play a dominating role in pacemaking in the sinoatrial node. The full text of this article is available at http://www.circresaha.org.
Honjo
H
H
Department of Humoral Regulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Inada
S
S
Lancaster
M K
MK
Yamamoto
M
M
Niwa
R
R
Jones
S A
SA
Shibata
N
N
Mitsui
K
K
Horiuchi
T
T
Kamiya
K
K
Kodama
I
I
Boyett
M R
MR
D000200:Action Potentials / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D022062:Electrophysiologic Techniques, Cardiac; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008839:Microelectrodes; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D012849:Sinoatrial Node / Q000166:cytology / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D007545:Isoproterenol; D002118:Calcium