This may be mediated:. This describes the peripheral nerve action potential. The heart is covered under the cardiac action potential. Excitable Cells. Excitable Cells Explain the basic electro-physiology of neural tissue, including conduction of nerve impulses and synaptic function. As the membrane is permeable to potassium, potassium will attempt to diffuse down this gradient, generating a negative intracellular charge which opposes further diffusion At some point, an electrochemical equilibrium is reached between: The concentration gradient dragging potassium out of the cell Negative electrical charge pulling it in This equilibrium is the resting membrane potential RMP is determined by: Permebility of the membrane to different ions Relative ionic concentrations on either side of the membrane Impermeable ions do not contribute to the resting membrane potential Altering membrane permeability causes a flow of ions and a change in voltage.
Nernst Equation The potential difference generated by a permeable ion in electrochemical equilibrium when there are different concentrations on either side of the cell can be calculated via the Nernst Equation : , where: is the equilibrium potential for the ion is the gas constant 8. This can be performed with the Goldman-Hodgkin-Katz equation : , where: is the permeability constant for the ion, If the membrane is impermeable to , then.
Note that: This model does not consider valency The concentrations of negative ions are reversed relative to positive ions Action Potential Excitable cells can respond to a stimulus by a changing their membrane potential. This may be mediated: Chemically e.
Fast sodium channels generate the all-or-nothing response: Stimuli below the threshold potential do not generate an action potential Stimuli above threshold potential generate an action potential The size of the stimulus does not affect the magnitude of the action potential, as this is determined by the fast sodium channels.
Occurs when the membrane potential reaches threshold potential. Occurs shortly after the open state, and lasts until the membrane potential falls below mV. Phases of the Action Potential This describes the peripheral nerve action potential. Membrane potential peaks at 30mV Falling Phase As potassium exits the cell, membrane potential continues to fall. This is the relative refractory period A large enough stimulus may overcome the additional hyperpolarisation and generate a second action potential.
The relative refractory period lasts ms Resting Cell is stable at resting membrane potential. The sinoatrial SA node is the normal site of origin of the electrical impulse action potential that stimulates heart muscle to contract. The SA node is located in the upper region of the right atrium.
Reproduced from wikipedia commons. The primary function of the heart is to transfer sufficient blood from the venous system to the arterial side of the circulation under sufficient pressure to maintain the circulatory needs of the body. As illustrated in Figure 2, the heart consists of four chambers which act as two separate pump systems. The atria, which sit dorsal to the ventricles are relatively thin walled, and their primary functions are to serve as a blood reservoir, and to assist in filling the ventricles with blood.
The ventricular chambers have much thicker walls the left being thicker than the right. The pattern with which the heart contracts and relaxes is cyclical, and is divided into a period of relaxation diastole , and a period of contraction systole. Figure 2. Basic anatomical features of the heart and pattern of blood movement. When the heart relaxes during diastole, blood passively drains into the atria, and through them into the ventricles. Contraction of the atria at the end of diastole assists in filling the ventricles. When the ventricles contract at the start of systole, the increase in pressure causes the closure of the tricuspid and mitral valves between the ventricles and atria associated with the first heart sound, S1.
Modified from wikipedia commons. The coordinated and synchronized contraction of the muscle cells in each chamber of the heart that occurs during each cardiac cycle of systole and diastole is achieved by a regular pattern of excitation that precedes each contraction. The time intervals that the cardiac impulse reaches each region of the heart during each beat of the cardiac cycle is illustrated in Figure 3. The normal pattern of excitation begins with the spontaneous appearance of action potentials in the Sinoatrial node SAN , which spontaneously generates action potentials at a frequency of per minute.
These action potentials spread rapidly through the left and right atria, and into the upper region of the atrioventricular node AVN. Conduction through the AVN is slow, requiring more than a hundred milliseconds. This delay provides enough time for the atria to contract and assist in filling the ventricles with blood before they are stimulated to contract. Once the impulse exits the distal end of the AVN it enters the bundle of His , which subsequently divides into left and right bundle branches that lie beneath the endocardial surface on each side of the ventricular septum.
Each bundle branch spreads downward from the base of the ventricle to the apex. These branches continuously divide into smaller Purkinje fibers that spread out and cover all parts of the ventricular endocardium. This causes them to contract at almost the same point in time. This coordinated contraction produces a reduction in ventricular volume that ejects blood across the valves into the pulmonary and systemic circulations. Figure 3. The pattern of transmission of the cardiac impulse through the heart during normal sinus rhythm.
Reproduced from the wikipedia commons. At the molecular level, intercalated discs consist of a group of gap junctions that provide a low-resistance electrical coupling between myocardial cells atrial or ventricular. This design allows the electrical currents produced by an action potential in one cell to excite depolarize neighboring cells to threshold, so that the excitation wavefront spreads through cardiac muscle atrial or ventricular in the direction that muscle fibers are oriented. Such cell-to-cell communication is necessary for producing a coordinated contraction of muscle cells within each cardiac chamber.
Gap junctions also permit the spread of metabolic or second messenger signals between cells. An increase in gap junctional resistance can slow conduction, but may also help protect healthy myocardium from being damaged by a neighboring region of myocardial ischemia by physically isolating healthy cells from ischemic cells which have pathologically low pH i , high Ca i and depolarized resting potentials analogous to closing the water tight doors to isolate the damaged region of a ship struck by a torpedo.
Figure 4. Schematic of a cross section of ventricular myocardium. Cardiac muscle cells are striated in appearance and roughly rectangular in shape. Myocardial cells are connected in series with each other by one or more intercalated discs, which consist of a very high density of low resistance gap junctions, comprised of connexin proteins that connect with connexin proteins on neighboring cells.
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These low resistance connections allow for the conduction of action potentials from one cell to another. The spread of depolarization and repolarization that takes place during each heart beat produces voltage changes that can be measured using electrodes placed on the surface of the body. The initial spread of depolarization across the right and left atria produces a voltage deflection called the P wave. The delay in conduction that takes place in the AV node produces a prolonged isoelectric pause after the P wave which comprises a major part of the PR interval Figure 5.
Changes in conduction time through the AV node, which can result from changes in autonomic tone, drug effects, or heart disease, will result in changes in the PR interval.
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Depolarization spreads from the endocardium where the Purkinje fibers terminate outward to the epicardium. Factors that affect the normal spread of depolarization in the ventricular myocardium sodium channel blocking drugs, myocardial ischemia, hyperkalemia will widen the QRS duration. The T wave reflects ventricular repolarization, and the QT interval reflects the time for complete ventricular repolarization. While the QT interval also includes the QRS interval the time for ventricular depolarization , clinically there are times when the QRS becomes oddly shaped, and fuses with the T wave, making it impossible to distinguish the end of the QRS with the beginning of the T wave.
Hence the QT interval is used as a convention to measure the time it takes for the ventricle to repolarize after the onset of depolarization. Events that abnormally prolong the QT interval K channel blocking drugs, mutations in ion channels - long QT syndrome are typically proarrhythmic by increasing the likelihood for multifocal ventricular arrhythmias such as Torsade de pointes , and are therefore potentially life threatening.
Because the duration of action potentials in the epicardium are shorter than in the endocardium, repolarization occurs first in the epicardium, followed by repolarization in the endocardium Figure 5. This causes the T wave to have an upright configuration.
The surface electrocardiogram can be measured from many different orientations e. Additional details will be provided in separate modules. Figure 5.
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Schematic representation of the heart, the electrocardiogram ECG , and action potentials recorded from different regions of the heart. The upstroke in cells outside the nodes is produced by the Na current. The duration of the atrial action potential is approximately one third that of ventricular action potentials.
Epicardial action potentials have a shorter duration compared to endocardial action potentials, and have a more pronounced phase 1 notch. These differences in action potential configuration result from regional differences in ion channel expression. The different components of the surface ECG reflect different events in the cardiac cycle as indicated by the color coding. The P wave reflects the time course for the spread of atrial depolarization. Cardiac action potentials have a complex shape that is distinctly different, and of much longer duration compared to those recorded from nerve or skeletal muscle.
By convention the cardiac action potential is subdivided into 5 distinct phases 0 through 4 see Figure 5. The phases are designated:. These different phases of the action potential result from the opening and closing of different voltage sensitive channels that selectively conduct different ions. As shown in Figure 5, the shape of the cardiac action potential is quite different when recorded from different regions of the heart. This results from the fact that cells in different regions express varying densities of the various ion channels that regulate the shape of the cardiac action potential.
Because of these differences in ion channel expression, cells from other regions differ from ventricular myocytes in that they lack a clear plateau phase e. SA node , or have a small or absent phase 1 component e. The cardiac action potential gains its peculiar shape from the opening and closing of different voltage sensitive channels. The flux of ions through each channel drives the membrane potential toward the equilibrium potential for that species of ion. In contrast, when heart cells are partially depolarized by an invading action potential, these K channels close, and a large number of excitable Na channels transiently open.
This non-inactivating component can be blocked by Na channel blocking drugs e. Other voltage and time-dependent inward and outward currents then become activated in a time-dependent sequence after phase 0. One of the first currents to become activated is the transient outward current I to , which produces a phase of rapid repolarization phase 1. The charge carrier for I to is K. The repolarizing effect of I to is counterbalanced by activation of the L-type Ca current, resulting in a plateau phase phase 2 of several hundred milliseconds where there is little change in voltage over time.
The behavior of many of these ion channels can be modulated by the presence of neurotransmitters, drugs and changes in metabolic conditions. Figure 6. Ionic basis for the resting and action potential in a ventricular heart cell.
The action potential is divided into phases 0 through 4. Each phase results from a change in the balance of inward and outward ionic currents that become activated upon membrane depolarization. The change in dominant conductance during each phase produce either net depolarization or hyperpolarization, and give the action potential its characteristic shape. Inward rectification describes the behavior of the channel to pass current most easily in the inward direction vs. Inward rectification can be caused by substances in the cytoplasm e. Having a longer action potential duration with a plateau phase is also important for excitation-contraction coupling which is regulated by calcium influx during phase 2.
Figure 7. Mechanism for inward rectification. In the absence of rectification dashed line , there would be a huge outward K current generated at positive voltages, producing a very short APD, and this would not allow time for Ca influx, which is necessary for excitation-contraction coupling to occur in cardiac muscle. Hence the resting potential can be predicted by the difference in extracellular and intracellular K concentrations according to the Nernst equation Figure 8.
In addition, myocardial ischemia produces a local tissue hyperkalemia that can reach levels of mM within a few minutes after the occlusion of a coronary artery Figure 8. Consequently, a common event during myocardial ischemia is a depolarization of the resting potential. This will be addressed in more detail in an upcoming module on cardiac arrhythmias. Figure 8. The relationship between extracellular potassium concentration [K] o and resting potential RP in a ventricular muscle cell. At lower K concentrations the relationship deviates from the Nernst relationship due to a limited permeability to other ions.
Note that hyperkalemia high [K] o results in membrane depolarization. The resting potential becomes zero when both internal and external [K] are equal.
Within a millisecond after Na channels open during phase 0, they enter into an inactivated closed state due to the rapid movement of an inactivation gate that shuts off the flow of Na ions through the channel. As illustrated in Figure 9, Na channels remain in this inactivated and inexcitable state throughout the action potential plateau until late during phase 3, when the membrane potential becomes sufficiently negative to cause a majority of Na channels to return to their rested excitable conformation.
Because of this voltage-dependent behavior, cardiac tissue cannot generate a second conducted action potential until a sufficient number of Na channels have regained their excitability by returning from the inactivated to rested states at the end of phase 3. This is an important characteristic of heart tissue in that it prevents the rapid re-excitation of the heart, which would preclude filling of the ventricles with blood.
The ERP. The ERP is defined as the time period during which cardiac cells remain inexcitable to a physiological stimulus following an action potential upstroke. The RRP. The relative refractory period is the time interval after the ERP during which conduction occurs, but at a less than maximal velocity. This phenomenon results from the fact that not all Na channels have recovered from inactivation during this time period. The time point at which virtually all Na channels have recovered from inactivation, and conduction velocity is maximal, designates the end of the RRP.
Figure 9. Changes in Na channel state during a typical action potential. At the end of diastole, all Na channels are in a rested state R. A second important consequence of the voltage-dependent gating of Na channels is that the fraction of Na channels that are free from inactivation at the beginning of an action potential upstroke depends upon the resting potential see Figure Cells having a depolarized resting potential positive to mV will have a reduced Na current amplitude and conduct action potentials slower than normal due to Na channel inactivation.
When the Na current is sufficiently reduced, complete block of conduction will occur. Depolarized resting potentials are a common feature of cardiac cells exposed to severe stretch, hyperkalemia, or ischemia. Excessive stretch of myocardial tissue can activate stretch-activated channels, which are non-selective for different ions, and therefore drive the resting membrane potential away from E K , and more towards 0 mV.
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Chronic depolarization of the RP that results in a reduction of Na current amplitude will reduce conduction velocity e. This topic will be explored in other modules. Figure Dependence of Na current amplitude on resting potential Na current availability curve. At normal or hyperpolarized resting potentials the majority of Na channels are in a rested state, and are available to be opened by a sudden depolarizing stimulus i.
This allows a maximal Na current to be elicited during conduction of the action potential. As the resting potential is made more depolarized, a progressively larger fraction of channels enter into an inexcitable inactivated state and cannot be reopened by a depolarizing stimulus. This results in a reduction in available Na current, and slower conduction. Cells exposed to pathological conditions often have depolarized resting potentials, leading to Na channel inactivation and conduction block. The rate and force with which the heart contracts is modulated by both the sympathetic and parasympathetic branches of the autonomic nervous system Figure The degree of basal tone neuronal stimulation on the heart is predominantly vagal vs.
Stimulation of sympathetic nerves increases heart rate, conduction velocity thru the AV node and the force of ventricular contraction. In contrast, stimulation of vagal nerves reduces heart rate and conduction velocity through the AV node, but does little to ventricular contractility. The distribution of sympathetic and parasympathetic nerves to the heart is asymmetrical, and as a consequence, stimulation of right vs. For example, stimulation of the right vagal nerve will produce a greater slowing of the sinus rate, while stimulation of the left vagus will produce a greater slowing of AV node conduction.
Clinically this is of little relevance, because both right and left vagal nerves are stimulated at the same time, but experimentally e. Anatomical distribution of autonomic nerves that regulate cardiac function. Sympathetic fibers from the left and right sides of the spinal column innervate both the atrium and ventricles. The sympathetic fibers from the right and left sides of the body are distributed asymmetrically to the various structures in the heart. Stimulation of sympathetic nerves on the right side produce larger increases in heart rate compared to stimulation of sympathetic nerves from the left side.
In contrast, stimulation of left sympathetic nerves produces a larger increase in ventricular contraction.