Korean Circ J.  2009 Jun;39(6):217-222. 10.4070/kcj.2009.39.6.217.

The Calcium and Voltage Clocks in Sinoatrial Node Automaticity

• Joung B
• Ogawa M
• Lin SF
• Chen PS

• KMID: 1490696
• DOI: http://doi.org/10.4070/kcj.2009.39.6.217

Abstract

Recent evidence indicates that the voltage (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release) jointly regulate sinoatrial node (SAN) automaticity. Since the intact SAN is a heterogeneous structure that includes multiple different cell types interacting with each other, the relative importance of the voltage and Ca2+ clocks for pacemaking may be variable in different regions of the SAN. Recently, we performed optical mapping in isolated and Langendorff-perfused canine right atria. We mapped the intracellular calcium (Cai) and membrane potentials of the intact SAN simultaneously. Using previously described criteria of the timing of the late diastolic Cai elevation (LDCAE) relative to the action potential upstroke to detect Ca2+ clock activity, we demonstrated that the sinus rate increased and the leading pacemaker shifted to the superior SAN with the robust LDCAE during beta-adrenergic stimulation. We also showed that the LDCAE was caused by spontaneous diastolic SR Ca2+ release and was closely related with heart rate changes. We conclude that the Ca2+ and voltage clocks work synergistically to generate SAN automaticity.

Keyword

Calcium; Sinoatrial node; Sarcoplasmic reticulum; Sympathetic nervous system

MeSH Terms

Action Potentials
Calcium
Heart Rate
Membrane Potentials
Membranes
Sarcoplasmic Reticulum
Sinoatrial Node
Sympathetic Nervous System
Calcium

Figure

• 

  Fig. 1 Activation pattern of SAN and surrounding RA during a 0.3 µmol/L isoproterenol infusion. A: isochronal map of Vm. The number on the each isochronal line indicates time (ms). The white-shaded area is the SAN. B: the Vm (blue) and Cai (red) recordings from the superior (a), middle (b), and inferior (c) SANs and the RA (d) are presented in A. C: magnified view of Cai and Vm tracings of the superior SAN. Note the robust LDCAE (solid arrow) before phase 0 of the action potential (0 ms), which in turn was much earlier than the onset of the p wave on ECG. D: the Vm and Cai ratio maps from -60 ms before to 180 ms after phase 0 of the action potential of C. The LDCAE (broken arrows in frames -40 and -20 ms) was followed by the Cai sinkhole during early diastole (solid arrow in frame 180 ms). This figure was reproduced with permission from Joung et al.29) SAN: sinoatrial node, RA: right atria, LDCAE: late diastolic Cai elevation.

• 

  Fig. 2 Co-localization of the LDCAE and leading pacemaker site. A: upward shift of the leading pacemaker site with the LDCAE during an isoproterenol infusion. (a) Cai ratio maps of SAN at each sinus rate. (b) corresponding Cai tracings from the superior (1, 2), middle (3, 4), and inferior (5, 6) SAN. At 95 bpm, sites 4 and 5 had the most prominent LDCAEs (*). As the sinus rate gradually increased, the sites of Cai elevation progressively moved upward. At the maximum sinus rate of 173 bpm, site 2 had the most apparent LDCAE. B: differential responses of different SAN sites to isoproterenol. (a) the Cai and Vm tracings from the inferior, middle, and superior SAN sites at different sinus rates. (b) the LDCAE and DD slopes of the superior SAN at different sinus rates. This figure was reproduced with permission from Joung et al.29) LDCAE: late diastolic Cai elevation, SAN: sinoatrial node, DD: diastolic dysfunction.

• 

  Fig. 3 Satellite stellate ganglion nerve activity (SGNA) and prolonged sinus pause. A: intermittent low amplitude burst discharge activity (LABDA) (arrows) associated with intermittently increased heart rate, and a large LABDA (*)-induced tachycardia. Sudden SGNA withdrawal resulted in a 5.5-s prolonged sinus pause. B: the data within the dotted line in panel A. vagal nerve activity (VNA). This figure was reproduced with permission from Ogawa et al.31)

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