title: Beat-to-beat Ca(2+)-dependent regulation of sinoatrial nodal pacemaker cell rate and rhythm.
abstract: Whether intracellular Ca(2+) regulates sinoatrial node cell (SANC) action potential (AP) firing rate on a beat-to-beat basis is controversial. To directly test the hypothesis of beat-to-beat intracellular Ca(2+) regulation of the rate and rhythm of SANC we loaded single isolated SANC with a caged Ca(2+) buffer, NP-EGTA, and simultaneously recorded membrane potential and intracellular Ca(2+). Prior to introduction of the caged Ca(2+) buffer, spontaneous local Ca(2+) releases (LCRs) during diastolic depolarization were tightly coupled to rhythmic APs (r²=0.9). The buffer markedly prolonged the decay time (T₅₀) and moderately reduced the amplitude of the AP-induced Ca(2+) transient and partially depleted the SR load, suppressed spontaneous diastolic LCRs and uncoupled them from AP generation, and caused AP firing to become markedly slower and dysrhythmic. When Ca(2+) was acutely released from the caged compound by flash photolysis, intracellular Ca(2+) dynamics were acutely restored and rhythmic APs resumed immediately at a normal rate. After a few rhythmic cycles, however, these effects of the flash waned as interference with Ca(2+) dynamics by the caged buffer was reestablished. Our results directly support the hypothesis that intracellular Ca(2+) regulates normal SANC automaticity on a beat-to-beat basis.
authors.affiliation: Laboratory of Cardiovascular Science, Gerontology Research Center, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD, USA.
authors.forename: Yael
authors.initials: Y
authors.lastname: Yaniv
authors.forename: Victor A
authors.initials: VA
authors.lastname: Maltsev
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Escobar
authors.forename: Harold A
authors.initials: HA
authors.lastname: Spurgeon
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Ziman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Stern
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
mesh_terms: D000200:Action Potentials; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D056966:Excitation Contraction Coupling; D011817:Rabbits; D012849:Sinoatrial Node / Q000378:metabolism / Q000502:physiology*
chemical_list: D002118:Calcium