Regulation+of+SA+Node


 * 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**" brings 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. 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. 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. 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. Cellular [|__hypoxia__] (usually due to [|__ischemia__]) depolarizes the membrane potential causing bradycardia; severe hypoxia completely stops pacemaker activity. 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. //Revised 11/03/2006//