Sympathetic Nerves Act on All Cardiac Cells to Cause Quicker, More Forceful Contractions
Sympathetic neurons release norepinephrine in all regions of the heart, not only at the SA and AV nodes, and all cardiac muscle cells have β-adrenergic receptors that are activated by norepinephrine.
Circulating epinephrine or norepinephrine can also activate these same receptors. The effects of β- receptor activation on the SA and AV node cells have already been described (see Figure 19-8 and Table 19-2). In all other atrial and ventricular cells, β-receptor activation leads to higher, shorter action potentials and to stronger, quicker contractions. One reason for these effects is that activation of β receptors increases the number of Ca2+ channels that open during the plateau (phase 2) of an action potential, which increases the amount of extracellular Ca2' that enters the ceil. Because Ca2+ entry is the primary depolarizing influence during the plateau, increased Ca2' entry raises the plateau (makes the membrane potential more positive). A secondary consequence is to shorten the action potential. The action potential becomes shorter because of a complicated effect of the elevated plateau on the K* channels. Recall that K+ channels close at the beginning of a cardiac action potential and then, after a time, reopen (see Figure 19-5). Reopening of the K* channels helps repolarize the cell to a resting state at the end of the action potential. The length of time before K* channels reopen depends on the membrane voltage during the plateau of the action potential. Specifically, when the membrane potential is more positive than normal during the plateau, the K+ channels reopen sooner. This shortens the action potential and speeds repolarization. Overall, β-receptor activation makes each action potential higher and shorter. An action potential of higher amplitude propagates more quickly along each cell and from cell to cell, leading to faster conduction velocity. The shorter action potential means a shorter refractory period, which facilitates formation of more heartbeats per minute.Because β-receptor activation opens more Ca2* channels and increases the entry of extracellular Ca2+ into cardiac muscle cells during an action potential, it also increases the strength of the resulting contraction. The entry of more extracellular “trigger” Ca2+ creates a greater stimulus for the release of Ca2+ stores from the sarcoplasmic reticulum. Therefore the cytosolic Ca2* concentration reaches an exceptionally high level during the action potential, which leads to a stronger contraction. The contraction also begins more quickly. In addition, the contraction is shorter, because β-receptor activation speeds up the pumps that move cytosolic Ca2* back into the sarcoplasmic reticulum and out of the cell into the extracellular fluid. Thus,even though more Ca2, than normal enters the cytosol during an action potential, its removal at the end of the action potential is quicker than normal. Overall, β-receptor activation makes each cardiac contraction stronger, quicker, and shorter.
In summary, sympathetic nerves act (1) on the SA node pacemaker cells to increase the heart rate, (2) on the AV node cells to increase the conduction velocity and shorten the AV delay, and (3) on all cardiac cells to shorten the refractory period and make each cardiac contraction stronger, quicker, and shorter. All these changes cause the heart to pump more blood at a higher pressure, which is an animal’s normal response during exercise or emotional arousal.
Because sympathetic effects on the heart are all brought about through activation of the β-adrenergic receptors on the cardiac muscle cells, the administration of a drug that activates β receptors (β-adrenergic agonist) has the same effects as sympathetic activation. Epinephrine and isoproterenol are two common β-adrenergic agonists. Conversely, the administration of a drug that binds to and blocks β receptors reduces all the effects of sympathetic activation. Propranolol and atenolol are common examples of such β-adrenergic antagonists. Examples of their use are provided later.