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 (r 2=0.9). The buffer markedly prolonged the decay time (T 50) 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.
Original language | English (US) |
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Pages (from-to) | 902-905 |
Number of pages | 4 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 51 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2011 |
Externally published | Yes |
Keywords
- Arrhythmia
- Ca cycling
- Ca2+-excitation contraction coupling
- Pacemaker Ca2+ clock
- Pacemaker cell automaticity
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine