title: Synergistic dual automaticity in sinoatrial node cell and tissue models.
abstract: BACKGROUND
  The mechanism of sinoatrial node (SAN) automaticity is traditionally attributed to membrane ion currents. Recent evidence indicates spontaneous sarcoplasmic reticulum (SR) Ca(2+) cycling also plays an important role.
  
  
  RESULTS
  A computer simulation on SAN cell and 1D tissue model was performed. In the SAN cells, SR Ca(2+) cycling broadly modulated the sinus rate from 1.74 Hz to 3.87 Hz. Shortening of the junctional SR refilling time and increase of SR Ca(2+) release were responsible for sinus rate acceleration. However, under the fast SR Ca(2+) cycling, decreased L-type Ca(2+) current (I(CaL)) resulted in irregular firing. When Ca(2+) cycling was suppressed, I(f) and I(CaT) both acted to stabilize the pacemaker rhythm, but I(CaT) had less effect than I(f). At the 1D level, the electrical coupling between neighboring cells had little effect on the earliest pacemaker location. The leading pacemaking site always colocalized with the site with the highest SR Ca(2+) cycling rate, but shifted to the site with less inhibited I(CaL).
  
  
  CONCLUSIONS
  The rate of SR Ca(2+) cycling can effectively and broadly modulate the sinus rate. I(f), I(CaL) and I(CaT) play integral roles to guarantee SAN cell rhythmic firing. The leading pacemaker site is determined by intracellular Ca(2+) dynamics and membrane currents, indicating the synergistic dual automaticity not only exists in single SAN cells, but also at the tissue level.
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Shinohara
authors.forename: Xi
authors.initials: X
authors.lastname: Mei
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
mesh_terms: D000818:Animals; D001683:Biological Clocks; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D003198:Computer Simulation; D007700:Kinetics; D008955:Models, Cardiovascular; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D002118:Calcium