Transmembrane action potential

Transmembrane action potential of a sinoatrial node cell. In contrast to other cardiac cells, there is no phase 2 or plateau. The threshold potential (TP) is -40 mV. The maximum diastolic potential (MDP) is achieved as a result of a gradual decline in the potassium conductance (gK+). Spontaneous phase 4 or diastolic depolarization permits the cell to achieve the TR thereby initiating an action potential (g = transmembrane ion conductance). Stimulation of pacemaker cells within the sinoatrial node decreases the time required to achieve the TR whereas vagal stimulation and the release of acetylcholine decrease the slope of diastolic depolarization. Thus, the positive and negative chronotropic actions of sympathetic and parasympathetic nerve stimulation can be attributed to the effects of the respective neurotransmitters on ion conductance in pacemaker cells of the sinuatrial node. gNa+ = Na+ conductance. 

The primary electrophysiological effects of moricizine relate to its inhibition of the fast inward sodium channel. Moricizine reduces the maximal upstroke of phase 0 and shortens the cardiac transmembrane action potential. The sodium channel blocking effect of moricizine is more significant at faster stimulation rates an action referred to as use dependence. This phenomenon may explain the efficacy of moricizine in suppressing rapid ectopic activity. An interesting effect of moricizine is its depressant effect on automaticity in ischemic... 

Coltart DJ, Meldrum SJ, Hamer J. The effect of propranolol on the human and canine transmembrane action potential. Br J Pharmacol 1970 40(1) 148P. 

Montero M, Schmitt C. Recording of transmembrane action potentials in chronic ischemic heart disease and dilated cardiomyopathy and the effects of the new class III antiarrhythmic agents D-sotalol and dofetilide. J Cardiovasc Pharmacol 1996 27(4) 571-7. 

Figure 1 is the current flow map for a two-dimensional cardiac tissue with nominal conductivity that arises from an assumed circular isochrone, where the rising phase of the transmembrane action potential in the radial direction was assumed to follow a typical behavior as given by the equation... 

Conductivity. Conductivity is an electrical property of excitable tissue which ensures that if one area of a membrane is excited to full activity, that area excites adjacent areas. Conduction of an impulse varies direcdy with the rate of development of phase 0 and the ampHtude of the action potential. Phase 0 is faster, and ampHtude of the action potential is greater, the more negative the transmembrane potential at the time of initiation of the impulse. Conduction velocity is faster when phase 0 is fast. 

Verapamil. Verapamil hydrochloride (see Table 1) is a synthetic papaverine [58-74-2] C2qH2 N04, derivative that was originally studied as a smooth muscle relaxant. It was later found to have properties of a new class of dmgs that inhibited transmembrane calcium movements. It is a (+),(—) racemic mixture. The (+)-isomer has local anesthetic properties and may exert effects on the fast sodium channel and slow phase 0 depolarization of the action potential. The (—)-isomer affects the slow calcium channel. Verapamil is an effective antiarrhythmic agent for supraventricular AV nodal reentrant arrhythmias (V1-2) and for controlling the ventricular response to atrial fibrillation (1,2,71—73). 

Antiarrhythmic Drugs. Figure 1 Transmembrane ionic currents of the cardiac action potential. In the middle of the figure, a typical cardiac action potential is shown as can be obtained from the ventricular myocardium (upper trace). Below, the contribution of the various transmembrane currents is indicated. Currents below the zeroline are inward currents above the zero line are outward fluxes. In the left column the name of the current is given and in the right column the possible clone redrawn and modified after [5]. 

Inward Rectifier Potassium Channels or Kir Channels are a class of potassium channels generated by tetra-meiic arrangement of one-pore/two-transmembrane helix (1P/2TM) protein subunits, often associated with additional beta-subunits. Kir channels modulate cell excitability, being involved in repolarization of action potentials (see Fig. 1), setting the resting potential (see Fig. 1) of the cell, and contributing to potassium homeostasis. 

The time course of an action potential reflects net current flow and thus the balance of open ion channels. The rate of change of membrane voltage is proportional to transmembrane current flow, according to the equation ... 

Fromm and Spanswick [79] found that electrical stimulation of a plant is followed by ion shifts which are most striking in the phloem cells. While their content of potassium and chloride was diminished after stimulation, the amount of cytoplasmic calcium increased slightly (Table 1). These displacements lead to the conclusion that Ca + influx as well as and CP efflux are involved in the propagation of action potentials. The main difference between propagation of action potentials in animals and plants is that in an axon there is the K /Na transmembrane transport but in phloem cells the K /Ca channels are involved in this process [Fig. 22(b)]. 

Slow-channel syndrome. Abnormally long-lived openings of mutant AChR channels result in prolonged endplate currents and potentials, which in turn elicit one or more repetitive muscle action potentials of lower amplitude that decrement. The morphologic consequences stem from prolonged activation of the AChR channel that causes cationic overload of the postsynaptic region - the endplate myopathy - with Ca2+ accumulation, destruction of the junctional folds, nuclear apoptosis, and vacuolar degeneration of the terminal. Some slow-channel mutations in the transmembrane domain of the AChR render the channel leaky by stabilization of the open state, which is populated even in the absence of ACh. Curiously, some slow-channel mutants can be opened by choline even at the concentrations that are normally present in serum. Quinidine, an open-channel blocker of the AchR, is used for therapy. 

An example of a ligand-gated ion channel (B) is the nicotinic cholinocep-tor of the motor endplate. The receptor complex consists of five subunits, each of which contains four transmembrane domains. Simultaneous binding of two acetylcholine (ACh) molecules to the two a-subunits results in opening of the ion channel, with entry of Na+ (and exit of some 1<+), membrane depolarization, and triggering of an action potential (p. 

Transmembrane ionic currents involve proteinaceous membrane pores Na+, Ca2+, and 1<+ channels. In A, the phasic change in the functional state of Na+ channels during an action potential is illustrated. 

The transient change in the transmembrane potential upon excitation. An action potential cycle consists of a transient depolarization of the cell membrane of an excitable cell (such as a neuron) as a result of increased permeability of ions across the membrane, followed by repolarization, hyperpolarization, and finally a return to the resting potential. This cycle typically lasts 1-2 milliseconds and travels along the axon from the cell body (or, axon hillock) to the axonal terminus at a rate of 1-100 meters per second. See Membrane Potential... 

Thus, a 10 1 transmembrane gradient of a single monovalent ion, say potassium, will generate a membrane potential of 58 mV. See Resting Potential Action Potential Depolarization Threshold Potential Nernst Equation Goldman Equation Patch-Clamp Technique... 

The transmembrane potential of cardiac cells is determined by the concentrations of several ions—chiefly sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl-)—on either side of the membrane and the permeability of the membrane to each ion. These water-soluble ions are unable to freely diffuse across the lipid cell membrane in response to their electrical and concentration gradients they require aqueous channels (specific pore-forming proteins) for such diffusion. Thus, ions move across cell membranes in response to their gradients only at specific times during the cardiac cycle when these ion channels are open. The movements of the ions produce currents that form the basis of the cardiac action potential. Individual channels are relatively ion-specific, and the flux of ions through them is... 

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