Effector Pathways To The Heart

Within the myocardium, parasympathetic nerve fibers release acetylcholine when stimulated. Cardiac cells contain muscarinic receptors embedded within their lipid bilayer, which can activate G proteins found in the cytoplasm upon binding with acetylcholine. Activation occurs when a bound GDP (gua-nosine diphosphate) molecule is replaced by a GTP (guanosine triphosphate) structure. Subsequently, this response allows the altered protein to bind with potassium channels in the membrane and causes them to open, thus increasing potassium permeability (Fig. 4). As a result, heart rate will generally decrease due to an efflux of potassium ions (K+) from cardiac cells because the cellular membrane becomes more polarized as the potential moves closer to the K+ equilibrium potential of -90 mV (6). This hyperpolarization makes the generation of action potentials more difficult and thus slows the rate of firing of the sinoatrial node. Activated G proteins will remain in such a state until GTP is hydrolyzed to form inactive GDP (2,11).

The type of regulatory control in the case described above involves the direct opening of K+ channels by G proteins within a cardiac muscle cell. It should also be noted that indirect opening of potassium channels may also occur after acetylcholine binds to the muscarinic receptors. Furthermore, activated G proteins may also cause some increase in the production of arachidonic acid, which acts as a secondary messenger that can result in increased K+ permeability caused by subsequent cleavage of membrane lipids (11).

Fig. 5. The effects of changes in sympathetic and parasympathetic outflow to the heart. The heart will increase its rate of contraction during increased sympathetic neural stimulation. This time is required for the cardiac pacemaker cells to reach threshold decreases. In contrast, increased parasympathetic outflow will decrease the heart rate and increase the time to threshold.

Fig. 5. The effects of changes in sympathetic and parasympathetic outflow to the heart. The heart will increase its rate of contraction during increased sympathetic neural stimulation. This time is required for the cardiac pacemaker cells to reach threshold decreases. In contrast, increased parasympathetic outflow will decrease the heart rate and increase the time to threshold.

The modulation of G proteins is also an important aspect of sympathetic effects on cardiac behavior. More specifically, sympathetic fibers release norepinephrine at postsynaptic terminals of cardiac muscle cells, and receptors located within the cellular membrane bind with the norepinephrine to stimulate a1 adrenergic receptors. Next, G proteins replace GDP at their binding sites with GTP when activated by the excited a1-receptors, causing an increase in the production of cyclic adenosine 5'-monophosphate (cAMP) within the cardiac myocytes. The increased cAMP levels cause molecules of protein kinase A to phosphorylate large numbers of calcium channels within the cellular membrane. This addition of a phosphate group not only causes Ca2+ channels to remain open longer, but also allows a greater number of channels to open, thus contributing to the influx of calcium ions into each cell on activation (6). In other words, the threshold for depolarization will be more easily attained because of the greater number of available calcium channels, thus allowing greater calcium incursion during activation and resulting in higher contraction strength.

An advantage of the mechanisms of action involving G proteins is that autonomic modulation can be sustained without constant nerve fiber stimulation. That is, a burst of synaptic activity causing the release of either acetylcholine or norepi-nephrine can initiate these aforementioned processes.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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