The general principles of skeletal muscle contraction also apply to cardiac and smooth muscle contraction but there are a number of interesting and important differences. Show
Structure of the HeartA human heart is a specialized muscular organ which beats over 2 billion times and pumps over 100 million gallons of blood over the course of the average human lifetime. Figure from Campbell's "Biology" 4th edition pg. 822. Fish have 2 chambers, one atrium and one ventricle. Fish hearts draw in deoxygenated blood in the atrium, and pump it out through a ventricle. Blood enters the heart, gets pumped through the gills and the oxygenated blood goes out to the body. Amphibians and reptiles have 3 chambers: 2 atria and a ventricle. (Crocodiles are the exception, as they have 4 chambers (2 atria, 2 ventricles). 3 chambered hearts have a complex circuit (blood from heart to lung and back to heart) and must be controlled so the blood travels from the heart to the lungs to become oxygenated and then pumped back the heart and out to the body. In the 3 chambered heart, a single ventricle pumps both out of the heart, and there is some mixing between oxygenated and deoxygenated blood. The bird and mammalian heart has four chambers: The insect heart is a simple tube. Heart contractions push the blood towards the head but because insects have an open circulatory system, there is no return circuit. The blood moves through the body cavity until it reaches the heart again. The earthworm has series of five chambers that make up its heart. Click on the image for a movie of earthworm heart function. Myogenic versus Neurogenic Cardiac muscleCardiac muscle (another type of striated muscle in vertebrates) has many similar properties to skeletal muscles but there are some important differences. Hearts of course vary greatly in size, shape and complexity from animal to animal - ranging from insects with a simple tube that pumps blood or hemolymph around an open circulatory system to our closed circulatory system and a four chambered heart. The basic principles that underlie cardiac muscle cell function though remain pretty much the same. 1) The heart contains pace-maker cells that produce the depolarization and action potentials to drive cardiac cell contraction. In other words heart contraction is not neuronally driven but self-driven or myogenically driven. (Of course there is an exception to every rule and some invertebrates the pacemaker cells are modified neurons that are attached to the heart). Some vertebrates hearts are innervated by neurons from the sympathetic and parasympathetic nervous systems but these neurons act in a modulatory function only. 2) Each muscle cell is a single cell not multinucleate like skeletal muscle. Like skeletal muscle cells each cell contains multiple myofibrils and in the cases of higher vertebrates an extensive sarcoplasmic reticulum and T-tubules. The SR and T-tubule system is not as extensive in animals with small cardiac muscle cells (myocytes) such as frogs and in many invertebrates. Therefore depending on the size of the cardiac muscle cells contraction can depend on Ca+2 release from the SR and/or Ca+2 influx from external sources outside the cell. This can be tested as removal of external Ca+2 strongly affects frog cardiac cell contraction but rat cardiac cells still can contract as they rely more on release from the SR. 3) Cardiac muscle cells are linked to each other with gap junctions. This allows an action potentials to rapidly travel from cell to cell and makes the heart work as a unit. This allows the pacemaker cells, the sinoatrial node cells, to generate the action potential which is in turn relayed via the gap junctions throughout the heart to generate contraction through out the heart. 3) There are different types of cardiac muscle cells ranging from the pacemaker cells in the sinoatrial node to the atrial and ventricular cells that produce the contraction of the heart chambers. All use the same mechanisms of excitation-contraction coupling but as we'll see there are distinct features to the sinoatrial cells that allow them to be pacemakers. 4) The action potential in cardiac cells is quite different from skeletal muscle and neuronal action potentials in that voltage-gated Ca+2 channels play a much larger role. See section on cardiac channels and action potentials 5) The mechanism of triggering the Ca+2 release channel in the sarcoplasmic reticulum is not the same as in vertebrate skeletal muscle cells. See section on Ca+2 release channels in the skeletal muscle lectures to review the differences between the two. Cardiac muscle channelsPumps and transporters - Cardiac cells also have the same types of pumps and transporters as skeletal muscle cells. In particular they have:
Channels - cardiac muscle cells share many of the same ion channels as neurons and skeletal muscle cells. Action potential in ventricular (and atrial) cardiac cellsFrom "Cell Physiology Source Book" The above diagram is an action potential recorded in the ventricular cardiac cell of the heart. The long Ca+2 plateau allows Ca+2 inside the cell to elevate enough to generate contraction in the case of those cardiac cells that rely on external Ca+2 sources. Action potential in sinoatrial cardiac cellsFrom "Cell Physiology Source Book" Sinoatrical cells have the ability to spontaneously fire action potentials in a repeated fashion without any external influence. These cells are the pacemaker cells of the heart and once an action potential fires in these cells it is propagated via gap junctions to other regions of the heart first to the atrial cells and then eventually making it to the ventricular cells. The generation of the action potential in these cells is very similar to the ventricular cardiac cells with a few major exceptions. The funny channel: This unusual cation channel is activated by hyperpolarization. As the membrane repolarizes after the action potential the threshold for opening of the funny channel is reached at about -50 mV. The channel opens and allows Na+ to perferentially flow into the cell. The funny channel is also called the HCN channel or hyperpolarization, cyclic nucleotide gated ion channel. As we will see cAMP can have dramatic influences on this channel and shift its threshold of activation from -50 mV to -40 mV. The funny channel actually looks very much like a voltage-gated K+ channel but has differences in its pore to allow Na+ influx and in the voltage sensing/opening mechanism. Putting it all together to get a heart beatThe excitatory and electrical conduction system of the heart is responsible for the contraction and relaxation of the heart muscle Human heart Located in the right atrium at the superior vena cava is the sinus node (sinoatrial or SA node) which consists of specialized muscle cells. The SA nodal cells are self-excitatory, pacemaker cells. They generate an action potential at the rate of about 70 per minute in humans (your heart beat). From the sinus node, activation propagates throughout the atria, but cannot propagate directly across the boundary between atria and ventricles, as noted above. This boundary serves to ensure a delay between the activation of the atria and the ventricles. In other words the impulse is delayed at this point to allow complete emptying of the atria before the ventricles contract. The atrioventricular node (AV node) is located at the boundary between the atria and ventricles. In a normal heart, the AV node provides the only conducting path from the atria to the ventricles. Propagation from the AV node to the ventricles is provided by a specialized muscle cells called the bundle of His conduct the signal system. Further down the bundle separates into two bundle branches which travel along each side of the septum, constituting the right and left bundle branches. Even more distally the bundles split into Purkinje fibers that branch and contact the inner sides of the ventricular walls. From the inner side of the ventricular wall, theese activation sites cause the formation of a wave of depolarization which propagates through gap junctions between the ventricular cells toward the outer wall. After each ventricular muscle region has depolarized, repolarization occurs. Electrocardiogram - ECGThe different potential generated in the heart can be measure using an electrocardiogram. An Electrocardiogram is a recording of the electric potentials being generated during heart activity. The potentials ("waves") are registered by electrodes placed on certain parts of the body and measure changes in potential (mV). Typically twelve electrodes are used placed in specific regions on the body.
An ECG curve reflects the perspective of the electrode recording it. The standard one seen below is from Standard Lead I, II and III. An ECG curve has different characteristics depending on the location of the electrode recording it. A negative deflection indicates that the recorded wave has traveled away from the electrode and a positive deflection means it has traveled towards it. Human heart and different potentials P wave - an impulse is generated at the sinoatrial node and spreads across both atria, causing them to contract. ECG of human heart and regions of contraction Modification of cardiac muscle function: Increased heart rateRelease of neurotransmitters from the autonomic nervous systems can increase or decrease heart contraction by directly affecting the funny channel or other ion channels in the membrane. Think about the physiological responses associated with adrenalin (epinephrine).
Epinephrine and norepinephrine: released from the sympathetic nervous system. Epinephrine and norepinephrine is synthesized and released into the blood by the adrenal medulla, an endocrine organ. Epinephrine and the related norepinephrine are all synthesized from tyrosine and contain the catechol moiety; hence they are referred to as catecholamines. Nerves that synthesize and use epinephrine or norepinephrine are termed adrenergic. Adrenergic receptors: bind epinephrine and norepinephrine. Because different receptors are linked to different G proteins, the activation leads to different signal transduction cascades. For instance, binding of norepinephrine to beta-adrenergic receptors on nerve cells causes activation of Gs and an increase in cAMP synthesis. Other neuronal adrenergic receptors activate Gi, Go, or other types of G proteins, resulting in a decrease in cAMP levels or increases in the levels of other intracellular second messengers, such as cGMP, inositol 1,4,5-trisphosphate (IP3), diacylglycerol, and arachidonic acid. Some second messengers, such as cGMP and IP3, act to directly open or close ion channels in neurons; IP3, for example, opens Ca2+ channels in the membrane of the endoplasmic reticulum, causing an increase in cytosolic Ca2+. Other second messengers have a more indirect effect on ion channel. In sinoatrial cells: norepinephrine binds to the b-adrenergic receptor which is a G protein associated membrane receptor. This triggers a signal transduction cascade outlined below that activates the G protein (Gs - stimulates) that activates adenylate cyclase to produce cAMP. Beta-blockers: Drugs which are used to slow heart contractions in the treatment of cardiac arrhythmia and angina, are beta1-adrenergic receptor antagonists. They bind the beta1-adrenergic receptor to block the receptor and thus slow heart contraction. Cardiac muscle cells possess beta1 adenergic receptors. The beta blockers usually have little effect on beta-adrenergic receptors on other cell types. The smooth muscle cells lining the bronchial passages possess b2 receptors, which mediate relaxation by binding catecholamines with the rank order of affinities isoproterenol >> epinephrine = norepinephrine. Agonists selective for b2 receptors, such as terbutaline, are used in the treatment of asthma because they specifically mediate opening of the bronchioles, the small airways in the lungs. Modulating the funny channelEffects of autonomic agonists on spontaneous activity and hyperpolarization-activated current (If) in cardiac sinoatrial node (SAN) myocytes from the rabbit. Spontaneous action potentials recorded in control conditions and in the presence of either isoprenaline (Iso) or acetylcholine (ACh). News Physiol Sci (2002) 17: 32-37. Through G protein coupled receptors various hormones/neurotransmitters or drugs can increase or decrease the heart rate by simply increasing or decreasing the ability of the funny channel to open.
The increase in cAMP physically binds to the funny channel and makes the channel open more easily. In other words the threshold for opening shifts from around -50 mV to around -40 mV. Therefore the funny channel will open sooner during the repolarization stage of the sinoatrial action potential and a second action potential will be triggered sooner. This means that a second wave of action potential and thus contraction will travel through the heart sooner ie. a faster heart rate. Modulation of Ca+2 channelEpinephrine also causes an increase in cAMP that stimulates PKA (protein kinase A) which in turn phosphorylates the voltage-gated Ca+2 channel (L channel). This phosphorylation results in a protein conformational change that enchances the channels activity. This new conformation of Ca+2 channel opens more readily (i.e. less time between action potentials) and opens for longer (i.e. more Ca+2 flow into the cell = greater [Ca+2] intracellular = greater contraction).
Caffeine: blocks the activty of phosphodiesterases. Phosphodiesterases break down cyclic nucleotides. Therefore in the presence of caffeine cAMP levels remain elevated and thus the funny channel continues to open more readily. Therefore the sinoatrial action potential fires more frequently and heart rate is increased.
Modification of cardiac muscle function: Decreased heart rateAcetylcholine: released from parasympathetic nervous system. Amanita muscaria. Source of plant steroid muscarine Muscarinic acetylcholine receptor: a G protein associated receptor. The G protein activated in this case is a Gi asubunit that inhibits adenylate cyclase. Modulating the funny channel
Acetylcholine works to block any rise in cAMP and reduces cAMP levels in the cell. Therefore the funny channel will now not open so readily and the slow depolarziation of the membrane will occur later thus resulting in a longer time to generate a second action potential. Effects of autonomic agonists on spontaneous activity and hyperpolarization-activated current (If) in cardiac sinoatrial node (SAN) myocytes from the rabbit. Spontaneous action potentials recorded in control conditions and in the presence of either isoprenaline (Iso) or acetylcholine (ACh). News Physiol Sci (2002) 17: 32-37. Modulating the voltage-gated K+ channels
Acetylcholine also works through the muscarinic receptor to stimulate the opening of a K+ channel. The muscarinic receptor stimulates the release of the G protein beta/gamma that directly activates a K+ channel. The opening of the channel suppresses the excitability of the membrane and thus suppresses muscle and heart contraction
DigitalisSpecifically Inhibits the Na+/K+ Pump by Blocking Its Dephosphorylation Digitalis, steroids from the dried leaf of the foxglove plant (Digitalis purpurea) Digitalis increases the force of contraction of heart muscle and is a drug used the treatment of congestive heart failure. Inhibition of the Na+/K+ pump by digitalis leads to a higher level of Na+ inside the cell. This results in a less favourable DeltaG for Na+ transport. The diminished Na+ gradient results in slower extrusion of Ca2+ by the sodium�calcium exchanger.
The increase in the intracellular level of Ca2+ enhances the contractility of cardiac muscle (remember contraction intensity is directly related to myoplasmic Ca+2 levels). Back to home Which neurotransmitter stimulates muscle cells to contract?Answer and Explanation: The neurotransmitter that stimulates muscle contraction is acetylcholine. Acetylcholine is the neurotransmitter of the neuromuscular junction, the connection between motor neurons and the skeletal muscle they control.
Which neurotransmitter excites skeletal muscle and inhibits cardiac muscle?Depending on the receptor, the same neurotransmitter may have excitatory effects at some synapses while having inhibitory effects at others. For example, acetylcholine excites skeletal muscle cells but inhibits cardiac muscle cells.
Which of the following is a major inhibitory neurotransmitter?GABA is the most common inhibitory neurotransmitter of your nervous system, particularly in your brain. It regulates brain activity to prevent problems in the areas of anxiety, irritability, concentration, sleep, seizures and depression.
What is the function of a neurotransmitter receptor in the dendritic membrane?In postsynaptic cells, neurotransmitter receptors receive signals that trigger an electrical signal, by regulating the activity of ion channels. The influx of ions through ion channels opened due to the binding of neurotransmitters to specific receptors can change the membrane potential of a neuron.
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