Action potential propagation

Normal rhythmic activity is the result of the activity of the sinus node generating action potentials that are conducted via the atria to the atrioventricular node, which delays further conduction to the His-Tawara-Purkinje system. From the Purkinje fibres, action potentials propagate to the ventricular myocardium. Arrhythmia means a disturbance of the normal rhythm either resulting in a faster rhythm (tachycardia, still rhythmic) or faster arrhythmia (tachyarrhythmia) or slowed rhythm (bradycardia, bradyarrhythmia). 

Class IC antiarrhythmic drugs such as flecainide or propafenone block the Na+ channel (open state propafenone open and inactivated state) with a very long dissociation time constant so that they alter normal action potential propagation. Flecainide increased mortality of patients recovering from myocardial infarction due to its proarrhythmic effects (CAST study). Action potential is shortened in Purkinje fibres but is prolonged in the ventricles. 

The action potential is propagated by local spread of depolarization. How does the action potential propagate smoothly down an axon, bringing new channels into play ahead of it Any electrical depolarization or hyperpolarization of a cell membrane spreads a small distance in either direction from its source by a purely passive process often called cable or electrotonic spread. The spread occurs because the intracellular and extracellular media... 

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. 

CNS development are employed for the same purpose in the PNS. PNS microglia-like cells, like microglia in the CNS, are bone-marrow-derived and have a similar repertoire of responses to activation [2], Both oligodendroglia and Schwann cells speed axonal action potential propagation by assembling and maintaining myelin. Capillary endothelial cells linked by tight junctions restrict entry of polar molecules into the PNS, as into the CNS [3],... 

The long duration of an individual uterine contraction in human (60—90 s) is difficult to explain using a single signalling mechanism. Myometrium clearly demonstrates action potential propagation, but this rapid (5 cm/s) mechanism... 

Young. I think gap junctions are very important in the initiation of labour. It has been shown that they increase the conduction rate of the action potential prior to the onset of labour. They seem to be induced prior to the initiating event in labour. You can have the gap junctions and the rapid action potential propagation, yet no spontaneous labour. Therefore they are necessary, but not sufficient. If I look at intercellular waves, as I flow the solution across, there is about a five cell communication that goes against the flow. In other words it has an intracellular mechanism, and it seems to be about four or five cells that go against the flow and the rest go with the flow. 

McHale What is your view of action potential propagation in the uterus in vivo, rather than in cultured cells ... 

Young In any calculation you allow for a number of variables in terms of trying to model the system of action potential propagation. We know that action potentials have to travel within a fasciculus, which is a macroscopic 1—2 mm connective tissue grouping of bundles. Those do not follow a very tortuous route, at the most they wind once or twice over 30 cm, but not much larger than that. The best simulation that s been done using action potential alone used around nine parameters and was totally unrealistic. I probably didn t point it out but the dashed line that overlayed my clinical contraction was where I actually assumed a 350 /tm size bundle. I assumed an intracellular Ca2+ wave and cell activity for 20 s, and I was able to fit it except for the foot at the end (Young 1997). 

Young RC 1997 A computer model of uterine contractions based on action potential propagation and intercellular calcium waves. Obstet Gynecol 89 604-608... 

L. B. Cohen. Changes in neuron structure during action potential propagation and synaptic transmission. Physiological Review, 53 373-413, 1973. 

Muscle contraction is triggered by motor neurons that release the neurotransmitter acetylcholine (see p. 352). The transmitter diffuses through the narrow synaptic cleft and binds to nicotinic acetylcholine receptors on the plasma membrane of the muscle cell (the sarcolemma), thereby opening the ion channels integrated into the receptors (see p. 222). This leads to an inflow of Na which triggers an action potential (see p. 350) in the sarcolemma. The action potential propagates from the end plate in all directions and constantly stimulates the muscle fiber. With a delay of a few milliseconds, the contractile mechanism responds to this by contracting the muscle fiber. 

Action potential propagation Local anesthetics, tetrodotoxin,1 saxitoxin2 Nerve axons Block sodium channels block conduction... 

Schematic diagram of a primary afferent neuron mediating pain, its synapse with a secondary afferent in the spinal cord, and the targets for local pain control. The primary afferent neuron cell body is not shown. At least three nociceptors are recognized acid, injury, and heat receptors. The nerve ending also bears opioid receptors, which can inhibit action potential generation. The axon bears sodium channels and potassium channels (not shown), which are essential for action potential propagation. Synaptic transmission involves release of substance P, a neuropeptide (NP) and glutamate and activation of their receptors on the secondary neuron. Alpha2 adrenoceptors and opioid receptors modulate the transmission process.

Lidocaine Blockade of sodium channels Slows, then blocks action potential propagation Short-duration procedures epidural, spinal anesthesia Parenteral duration 30-60 min 2-6 h with epinephrine Toxicity CNS excitation... 

Morley GE, Anumonwo JMB, Delmar M Effects of 2,4-dinitrophenol or low [ATP on cell excitability and action potential propagation in guinea pig ventricular myocytes. Circ Res 1992 71 821-830. 

FIGURE 12-3 Schematic diagram showing mechanism of action of local anesthetics on the nerve membrane. Local anesthetics appear to bind directly to a site within the sodium channel, thereby locking the channel in a closed position, thus preventing sodium entry and action potential propagation. 

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