Figure 38.4 The Autonomic Nervous System Controls Heart Rate
There has been considerable research on the mechanisms that affect heart rate. Control lies within the pacemaker cells of the sinoatrial node, but what is the role of the autonomic nervous system? To understand ANS influence on pacemaker cells, one can measure membrane potentials in pacemaker cells, as well as those cells treated with the neurotransmitters norepinephrine and acetylcholine. Compared to the untreated controls, norepinephrine causes an increase in the rate of membrane depolarization, resulting in an increase in heart rate. By contrast, acetylcholine decreases the rate of membrane depolarization, resulting in a decreased heart rate. Pacemaker depolarization is initiated by the if current, first discovered in 1979 by Brown, Difrancesco, and Noble. The if current operates via ion channels referred to as f-channels. Activity of f-channels is modulated by cAMP; thus, these channels are affected by norepinephrine, which increases cAMP, and acetylcholine, which decreases cAMP. Norepinephrine is released by the sympathetic nervous system and coordinates the “fight or flight” response to certain, often dangerous, situations. On the other hand, acetylcholine is part of the parasympathetic nervous system and acts to return the body to normal after a sympathetic response. Thus, it makes sense that norepinephrine results in increased heart rate, whereas acetylcholine slows the heart rate down, returning it to normal. Continued understanding of the cellular control of f-channels has led to the development of therapies to address various heart disorders. Many heart problems are due to defects in these f-channels; people with electronic pacemakers often have problems with these channels, suggesting the possibility of gene therapy to create biologically engineered pacemakers. Further, various drugs have been developed that are f-channel blockers, slowing the heart rate when such a therapy is warranted. Given the magnitude of heart disease worldwide, further understanding of the mechanism of pacemaker activity at the cellular level is an active area of research that will likely provide the basis for future therapies.
Original Papers
Grodner, A. S., H.-G. Lahrtz, P. E. Pool, and E. Braunwald. 1970. Neurotransmitter Control of Sinoatrial Pacemaker Frequency in Isolated Rat Atria and in Intact Rabbits. Circulation Research 27: 867–873.
http://circres.ahajournals.org/cgi/content/abstract/27/6/867
Levy, M. N. 1971. Brief Reviews: Sympathetic-Parasympathetic Interactions in the Heart. Circulation Research 29: 437–445.
http://circres.ahajournals.org/cgi/reprint/29/5/437.pdf
Carrier, G. O., and V. S. Bishop. 1972. The interaction of acetylcholine and norepinephrine on heart rate. Journal of Pharmacology and Experimental Therapeutics 180: 31–37.
http://jpet.aspetjournals.org/cgi/content/abstract/180/1/31
Brown, H. F., D. Difrancesco, and S. J. Noble. 1979. Cardiac pacemaker oscillation and its modulation by autonomic transmitters. Journal of Experimental Biology 81: 175–204.
http://jeb.biologists.org/cgi/reprint/81/1/175
Brown, H. F., D. Difrancesco, and S. J. Noble. 1979. How does adrenaline accelerate the heart? Nature 280: 235–236.
http://www.nature.com/nature/journal/v280/n5719/abs/280235a0.html
Links
Mangoni, M. E., and J. Nargeot. 2008. Genesis and regulation of the heart automaticity. Physiological Reviews 88: 919–982.
http://dx.doi.org/10.1152/physrev.00018.2007
DiFrancesco D. 2005. Cardiac pacemaker If current and its inhibition by heart rate-reducing agents. Current Medical Research and Opinion 21: 1115–1122.
http://dx.doi.org/10.1185/030079905X50543
Kryzhanovskii, S. A., and M. B. Vititnova. 2009. Heart rate control: f-channel blockers. Human Physiology 35: 230–240.
http://dx.doi.org/10.1134/S0362119709020145
Kimball’s Biology Pages: The Heartbeat
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/Heart.html
University of Washington School of Medicine: The Heart: an important ANS effector
http://courses.washington.edu/chat543/cvans/sfp/effector.html
University of Milan: Laboratory of Molecular Physiology and Neurobiology: PaceLab
http://users.unimi.it/difrancesco/Lab_eng.html