The pacemaker (sinoatrial node, SAN) is a patch of specialized, excitatory cells embedded in the inner wall of the right atrium. "Bottom line up front" is that the repetitive production of a brief, positive spike in the action potential (AP) of these cells is the cause of the onset of each beat of the heart. The frequency with which these AP spikes occur can be modified by the activity of the two divisions of the autonomic nervous system (ANS); sympathetic (SNS) activity increases the heart rate while parasympathetic (PSNS) activity decreases it.
The membrane components of the diagram are situated on a large dotted circle representing a cell membrane. At the very top is a small grey ATP circle representing sodium/potassium pumps that move 2 K+ into the cell and 3 Na+ out (arrows labeled 2 and 3). To the left, a K+ is shown leaving the cell (purple arrow) through a Kr channel. A portion of the AP graph is shown within the cycling potassium ions; the purple part of the curve depicts this loss of positive charge (K+) due to this potassium current.
KACh (pink) is a type of potassium channel stimulated (+) by the PSNS that increases the overall potassium current as indicated by the pink arrow that joins the purple one. This increase in the potassium current causes a more negative mean diastolic potential (MDP) as suggested by the pink line in the graph.
To the right of the sodium/potassium pump is a section of the AP graph (light blue) called early diastolic depolarization that occurs after repolarization. HCN channels (light blue) allow the diffusion of Na+ into the cell creating a sodium current (light blue arrow). This gain of positive charge changes the direction of the AP curve from downward to upward. The sodium ions are later removed from the cell by the sodium/potassium pumps as shown by the black '3' arrow.
There is a long black arrow pointing to (+) beside the HCN channel. The arrow arises from cAMP within the cytoplasm. The (+) symbol indicates that when cAMP is present it stimulates the HCN channels to open sooner than usual and also increases the sodium current.
The red arrow indicates Ca2+ entering the cell through CaT channels; these are the first to activate the exchanges (dashed arrow between Ca2+ and NCX). A second source of 'activating' Ca2+ is the sarcoplasmic reticulum (SR, mushroom). This organelle cyclically releases small spurts of Ca2+ called local calcium releases (LCR purple arrow).
These events cause the AP curve to change from linear to exponential as indicated by the green line in the graph.
The final section of the AP graph (blue) shows an incoming Ca2+ current (blue arrow) through CaL channels. This large calcium current causes a sharp rise in the AP curve (blue line in graph) by further activating sodium calcium exchangers (blue arrow) to increase the influxing sodium current and also stimulate (blue arrow) RyR2 channels in the SR to open and release stored Ca2+ (CICR purple arrow) that also are removed by the exchangers. Calcium ions that are not moved out of the cell by the exchangers are moved back into the SR via SERCA pumps (purple arrow). If the cytoplasmic concentration of Ca2+ becomes too high these ions are removed from the cell (thin blue arrow) by calcium pumps (grey ATP circle) in the cell membrane.
The concentration of cyclic adenosine monophosphate (cAMP) is dependent on the relative activities of the sympathetic (SNS) and parasympathetic (PSNS) divisions of the autonomic nervous system. Epinephrine (E) and/or norepinephrine (NE) bind to membrane-bound beta receptors that cause the activation (+) adenyl cyclase (AC); acetylcholine (ACh) binds to membrane-bound muscarinic 2 receptors that inactivate (-) AC.
The extent of activation of membrane-bound AC governs the the extent of conversion of ATP to cAMP (curved arrow touching grey AC circle). As indicated by dashed arrows, cyclic AMP:
The cytoplasmic PKA that is activated by cAMP (dashed arrow) causes additional effects indicated by dashed arrows. It:
Last updated: 2/14/2016
Continue to Phases
Return to home page