A similar response is noted when a drug such as atropine is administered. This drug blocks vagal influences at the SA node by antagonizing the muscarinic receptors that bind to acetylcholine, which is the neurotransmitter released by the vagus nerve. For heart rate to increase during physical activity, the medullary centers controlling autonomic function reduce vagal efferent activity and increase sympathetic efferent activity to the SA node.
High heart rates cannot be achieved in the absence of vagal inhibition. 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 at the SA node.
Norepinephrine released by sympathetic activation of the SA node binds to beta-adrenoceptors. This increases the rate of pacemaker firing primarily by increasing the slope of phase 4 , which decreases the time to reach threshold.
Sympathetic activation also lowers the threshold for initiating phase 0 of the action potential. These changes in ion currents decrease the slope of phase 4 of the action potential, thereby increasing the time required to reach threshold. It is concluded that the slow-onset long-lasting response of the SA node cell membrane to ACh may play a role in the phase-dependent effect of vagal stimulation.
Abstract The effects of vagal stimulation on the activity of the isolated rabbit sino-atrial SA node preparation were studied using electrophysiological techniques.
Phosphorylation of myosin also occurs, increasing the rate of cross bridge cycling. Catecholamines also increase the rate of re-uptake of calcium into the sarcoplasmic reticulum, thus aiding relaxation. This increases during exercise. Oxygen extraction from blood in the coronary circulation is high; therefore, an increase in oxygen demand must be met by an increase in coronary blood flow.
The heart is very versatile in its use of metabolic substrates. Glucose and lactate are used in roughly equal proportions. The proportion of substrates utilized may vary depending on the nutritional state of the person.
After a large meal containing glucose, more pyruvate and lactate are used. During periods of starvation, more fat is utilized. Insulin enhances glucose uptake into cardiac myocytes, and in untreated diabetes proportionally more fat is utilized. This proportion increases during periods of hypoxaemia; however, lactic acidosis impairs myocardial function and can ultimately lead to myocardial cell death.
The mechanics of cardiac myocyte contraction can be studied in the laboratory by examining the behaviour of an isolated muscle strip Fig. The papillary muscle is convenient for this as its fibres run in roughly the same direction. The muscle is placed under an initial tension or preload. If the muscle strip is anchored at both ends and stimulated it undergoes isometric contraction. The tension generated during isometric contraction increases with increasing initial length Fig.
Alteration in initial fibre length is analogous to preload. Increasing venous return to the heart results in an increased left ventricular end diastolic volume, thereby increasing fibre length. This produces an increase in the force of contraction and an increased stroke volume resulting in the familiar Starling curve. The conventional explanation for this is that at normal resting length, the overlap of actin and myosin is not optimal.
Increasing the initial length improves the degree of overlap and therefore increases the tension developed. It has become clear in recent years that this mechanism is unlikely to account for the shape of the Starling curve under physiological conditions. Several other possible mechanisms have been implicated.
Lengthening the muscle increases the sensitivity of troponin to calcium length-dependent calcium sensitivity and can also lead to enhanced intracellular free calcium. Contractile properties of myocardial muscle. Left: Simplified arrangement to study contraction of isolated cat papillary muscle. The weight labelled preload sets the resting length. If the preload is clamped in place contraction becomes isometric.
Right: Three fundamental relations: a isometric contraction at increasing lengths, b and c isotonic contractions beginning from two different resting lengths 8 and 10 mm. Contractile force, velocity, and shortening are all increased by stretching the relaxed muscle.
If the muscle is able to shorten, but has to lift a weight, this is known as isotonic contraction. The weight moved by the muscle strip represents afterload. As afterload increases, both the amount and velocity of shortening decreases Fig. Conversely, reducing the afterload enhances shortening, a fact of considerable importance in the management of the failing heart. If the preload is increased by stretching the muscle and the experiment repeated, both velocity and shortening are enhanced.
In vivo , the initial phase of cardiac contraction, from the closure of the mitral and tricuspid valves to the opening of the aortic and pulmonary valves, is isotonic. Tension is developed, but the ventricle does not eject blood, as there is no muscle fibre shortening.
After the opening of the aortic and pulmonary valves, contraction becomes isotonic, tension is maintained, but blood is ejected and tonic shortening occurs. In vitro , perfusing papillary muscles with norepinephrine increases the strength and rapidity of the isometric contraction.
This increased contractility i. As mentioned earlier, catecholamines may augment both contraction and relaxation of cardiac muscle. However, as catecholamines increase the intracellular calcium load, more energy is required to fuel the pumps that sequester the calcium in diastole. The SA node is supraventricular and is sensitive to parasympathetic and sympathetic influence.
Finally, healthy contractile myocytes have the necessary equipment for automaticity but they require a much greater negative resting voltage to initiate a spontaneous action potential.
Pacemakers myocytes depolarize and repolarize in a series of electrical phases. The ions move across the cell membrane through ion channels. Some channels are always open and their specific ions can move freely from high concentration to low concentration.
When a channel is opened, ions specific to that ion channel move from high concentration to low concentration. Closure of an ion channels decrease ion influx or efflux. As ions flow through open channels, they alter the distribution of charge across the membrane.
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