Action potential velocity

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. 

Glass IB Antiarrhythmic Agents. Class IB antiarrhythmic agents produce less inhibition of the inward sodium current than Class lA agents. In normal myocardial tissue, phase 0 may be unaffected or minimally depressed. However, in ischemic or infarcted tissue, phase 0 is depressed. Myocardial tissue exposed to Class IB agents exhibits decreased automaticity, shortened action potential duration, ie, shortened repolarization, and shortened refractory period. Excitability of the myocardium is not affected and conduction velocity is increased or not modified. The refractory period is shortened less than its action potential duration, thus the ratio of refractory period to action potential duration is increased by these agents. The net effect is increased refractoriness. The PR and QT intervals of the ECG are shortened and the QRS interval is unchanged (1,2). 

Action potentials, self-propagating. Action potentials of smooth muscle differ from the typical nerve action potential in at least three ways. First, the depolarization phases of nearly all smooth muscle action potentials are due to an increase in calcium rather than sodium conductance. Consequently, the rates of rise of smooth action potentials are slow, and the durations are long relative to most neural action potentials. Second, smooth muscle action potentials arise from membrane that is autonomously active and tonically modulated by autonomic neurotransmitters. Therefore, conduction velocities and action potential shapes are labile. Finally, smooth muscle action potentials spread along bundles of myocytes which are interconnected in three dimensions. Therefore the actual spatial patterns of spreading of the action potential vary. 

The velocities of the propagation of electrical signals that have values from 0.0005 to 40m/s are sufficiently high to facilitate rapid long-distance communication and account for the rapid response phenomena observed in plants. Both the speed of propagation and the duration of action potential depend on the type of external stimulus. 

FIG. 2 Measurements of intracellular potentials in sieve tubes of maize via severed aphid stylets. Stimulation by ice water (above) and electric shock (below) evoked action potentials which were propagated with a velocity of 3-5cms in a basipetal direction. (From Ref. 36.)... 

The fastest velocity reported for transmission of action potentials in green plants was 0.2 m/s in Dionaea flytrap [11]. Action potentials induced in soybean by FCCP are 200 times... 

A second factor that influences the velocity of action potential conduction is the diameter of the axon. The greater the diameter is then, the lower the resistance to current flow along the axon. Therefore, the impulse is... 

Verapamil (Class IV antiarrhythmic drug) is an effective agent for atrial or supraventricular tachycardia. A Ca++ channel blocker, it is most potent in tissues where the action potentials depend on calcium currents, including slow-response tissues such as the SA node and the AV node. The effects of verapamil include a decrease in heart rate and in conduction velocity of the electrical impulse through the AV node. The resulting increase in duration of the AV nodal delay, which is illustrated by a lengthening of the PR segment in the ECG, reduces the number of impulses permitted to penetrate to the ventricles to cause contraction. 

Procainamide (Class IA antiarrhythmic drug) is an effective agent for ventricular tachycardia. Its mechanism of action involves blockade of the fast Na+ channels responsible for phase 0 in the fast response tissue of the ventricles. Therefore, its effect is most pronounced in the Purkinje fibers. The effects of this drug s activity include a decrease in excitability of myocardial cells and in conduction velocity. Therefore, a decrease in the rate of the phase 0 upstroke and a prolonged repolarization are observed. As a result, duration of the action potential and the associated refractory period is prolonged and the heart rate is reduced. These effects are illustrated by an increase in the duration of the QRS complex. 

In axonal neuropathies, the velocity of action potential propagation in surviving axons is well maintained but the number of axons capable of conducting action potentials is diminished. Transcutaneous nerve stimulation and recording, the method routinely used for studying nerve conduction in the clinic, does not permit evaluation of the function of autonomic or unmyelinated sensory axons. These smaller, slow-conducting axons can be analyzed, in research studies, by intraneural recording with needle electrodes. 

A decrease in the amplitude of the sensory nerve action potential has also been observed in a group of 20 asymptomatic workers exposed to -hexanc (Pastore et al. 1994). The subjects of this study were selected on the basis of urinary levels of the n-hexane metabolite 2,5-hexanedione (See Sections 2.3 and 2.7) exceeding 5 mg/L and compared to a group of unexposed laboratory workers. Mean years worked was 8.13 (range, 1.5—23 years). Sensory and motor nerve conduction velocities and distal latencies were normal in all nerves tested. However, significant decreases were found in sensory nerve action potential amplitude in the median, sural, and ulnar nerves. Neither the level of 2,5-hexanedione in urine nor age correlated with the changes in amplitude however, there was a significant correlation between years worked and amplitude. 

Co-exposure to -hexane and xylene resulted in a loss of auditory sensitivity in male Sprague-Dawley rats (Nylen et al. 1994) as measured by the auditory brainstem response. Exposure to -hexane or xylene alone at 1,000 ppm for 61 days for 18 hours a day caused a slight loss of auditory sensitivity when measured 2 days after the end of exposure. Simultaneous exposure to w-hexane and xylene (1,000 ppm each) caused a greater and persistent loss of auditory sensitivity which was greater than the sum of effects of exposure to w-hexane and xylene separately. These effects were still observed 4 and 10 months after exposure ended. In contrast, combined exposure to -hexane and xylene partially reversed the decreased nerve conduction velocities and action potential amplitudes observed in the group treated with 77-hexane alone. These effects were persistent from 2 days to 10 months after cessation of exposure. 

CVSF = conduction velocity of slow = motor fibers dSCV = distal sensory nerve conduction velocity MAP k/a = proximal to distal amplitude ratio of muscle action potentials MMCV = maximal motor nerve conduction velocity MNCV = mixed nerve conduction velocity RL = residual latency of motor nerve conduction... 

Sodium fluoroacetate (but not methyl fluoroacetate) is practically without action on frog nerve or brain in vitro. The ester decreases the action potential of frog sciatic nerve and reduces the conduction velocity.5 The inactivity of the salt may be related partly to its inability to penetrate cells. 

In myelinated peripheral nerves, the sheath is intenupted by small gaps, the nodes of Ranvier. It is these nodes that increase markedly the velocity of the action potential as it travels along the axon (see below). Myelinated and nonmyelinated axons, together with their Schwann cells, are shown in Figure 14.1. 

Cardiostimulation. By stimulating Pi-receptors, hence activation of ade-nylatcyclase (Ad-cyclase) and cAMP production, catecholamines augment all heart functions, including systolic force (positive inotropism), velocity of shortening (p. clinotropism), sinoatrial rate (p. chronotropism), conduction velocity (p. dromotropism), and excitability (p. bathmotropism). In pacemaker fibers, diastolic depolarization is hastened, so that the firing threshold for the action potential is reached sooner (positive chronotropic effect, B). The cardiostim-ulant effect of p-sympathomimetics such as epinephrine is exploited in the treatment of cardiac arrest Use of p-sympathomimetics in heart failure carries the risk of cardiac arrhythmias. 

In a 10-month study, monkeys exposed to 1,000 ppm 2-hexanone had abnormal results in electrodiagnostic tests (Johnson et al. 1977). There was a progressive and statistically significant decrease in the maximum motor conduction velocity of the sciatic-tibial nerves starting at 4 months of exposure and a decrease in the maximum conduction velocity of the ulnar nerves starting at 1 month. Decreased amplitude of evoked muscle action potential was also seen at 1,000 ppm. 

Mechanism of action - Disopyramide is a class lA antiarrhythmic agent that decreases the rate of diastolic depolarization (phase 4), decreases the upstroke velocity (phase 0), increases the action potential duration of normal cardiac cells, and prolongs the refractory period (phases 2 and 3). It also decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium and does not affect alpha- or beta-adrenergic receptors. 

A next-level assay is usually an isolated heart/cardiac tissue preparation. The canine Purkinje fiber assay (GLP) measures several action potential parameters, like resting membrane potential, upstroke velocity, action potential duration and shape, but also if a drug acts reverse-use dependently [72]. Based on changes of the action potential shape it is possible to conclude which ion channels are modulated (e.g., L-type calcium channel block would abolish the plateau phase). The papillary muscle assay (e.g., guinea pigs) determines similar parameters [73]. 

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