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Regulation of Pacemaker Activity
 The SA node displays intrinsic automaticity (spontaneous pacemaker activity) at a rate of 100-110 action
potentials ("beats") per minute. This intrinsic rhythm is primarily influenced
by autonomic nerves, with vagal influences being dominant
over sympathetic influences at rest. This "vagal tone"
reduces the resting heart
rate down to 60-80 beats/min. The SA node is predominantly innervated by
efferent branches of the right vagus nerves, although some innervation from the
left vagus is often observed. Experimental denervation of the right vagus
to the heart leads to an abrupt increase in SA nodal firing rate if the
resting heart rate is below 100 beats/min. A similar response is noted when a
drug such as atropine
is administered. This drug blocks vagal transmission at the SA node by
antagonizing the
muscarinic receptors that bind to acetylcholine, which is the
neurotransmitter released by the vagus nerve.
 Parasympathetic (vagal) activation, which
releases acetylcholine (ACh) onto the SA node, decreases pacemaker rate by increasing gK+
and decreasing slow inward gCa++ and gNa+; the pacemaker
current (If) is suppressed. These
ionic conductance changes decrease the slope of phase 4
of the action potential, thereby increasing the time required to reach threshold. Vagal
activity also hyperpolarizes the pacemaker cell during Phase 4, which results in a longer
time to reach threshold voltage.
The rate of SA nodal firing can be altered by:
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changes in autonomic nerve activity
(sympathetic and vagal)
To increase heart rate, the
autonomic nervous system increases sympathetic outflow to the SA node, with
concurrent inhibition of vagal tone. Inhibition of vagal tone is necessary
for the sympathetic nerves to increase heart rate because vagal influences
inhibit the action of sympathetic nerve activity. Sympathetic activation, which releases
norepinephrine (NE), increases pacemaker rate by decreasing gK+ and
increasing slow inward gCa++ and gNa+; the pacemaker
current (If) is enhanced. These changes increase the
slope of phase 4 so that the pacemaker potential more rapidly reaches the
threshold for action potential generation.
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circulating hormones
Pacemaker activity is also altered by hormones. For example,
hyperthyroidism induces tachycardia and hypothyroidism induces
bradycardia. Circulating
epinephrine causes tachycardia by a mechanism
similar to norepinephrine released by sympathetic nerves.
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serum ion concentrations
Changes in the serum concentration of ions,
particularly potassium, can cause
changes in SA nodal firing rate. Hyperkalemia induces bradycardia or can even stop SA nodal
firing. Hypokalemia increases the rate of phase 4 depolarization and causes tachycardia. It apparently does this by
decreasing gK during
phase 4.
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cellular hypoxia
Cellular hypoxia (usually due
to ischemia) depolarizes the membrane potential causing
bradycardia; severe hypoxia completely stops pacemaker activity.
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drugs
Various drugs used as antiarrhythmics also affect SA
nodal rhythm. Calcium-channel blockers, for example, cause bradycardia by inhibiting the slow inward Ca++ currents during
phase
4 and phase 0. Drugs
affecting autonomic control or autonomic receptors (e.g.,
beta-blockers,
muscarinic antagonists) directly or indirectly alter
pacemaker activity.
Digitalis causes bradycardia by increasing parasympathetic
(vagal) activity on the SA node; however, at toxic concentrations, digitalis
increases automaticity and therefore can cause
tachyarrhythmias. This toxic effect is related to the inhibitory effects
of digitalis on the membrane Na+/K+-ATPase, which
leads to cellular depolarization, increased intracellular calcium, and changes
in ion conductances.
Pacemaker activity is influenced dramatically by
age. The maximal heart rate that can be achieved in an individual
is estimated by
Maximal Heart Rate @
220 beats/min – age in years
Therefore a 20-year-old person will have a maximal heart rate
of about 200 beats/min, and this will decrease to about 170 beats/min when the person is
50 years of age. This maximal heart rate is genetically determined and cannot be modified
by exercise training or by external factors.
RK Revised
04/06/2007
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Cardiovascular Physiology Concepts
