Threshold potential, neurons

Purkinje cells is demonstrated in Figure 12.1 and, like all cardiac myocytes, can be divided into four phases. Phase 4 (pacemaker potential) involves the slow influx of sodium ions, depolarizing the cell until the threshold potential is reached. Once the threshold potential is reached, the fast sodium current is activated, resulting in a rapid influx of sodium ions causing cell depolarization (phase 0 rapid depolarization). Phase 1 (partial repolarization) involves the inactivation of sodium channels and a transient outward current. Phase 2 (plateau phase) results from the slow influx of calcium ions. Repolarization (phase 3) occurs as a result of outflow of potassium ions from the cell and restores the resting potential. There are variations between the different areas of the heart, specifically the nodal tissues do not possess fast sodium channels and slow L-t5rpe calcium channels generate phase 0 current (Fig. 12.1). Phase 4 activity varies between nodal areas the sinoatrial node depolarizes more rapidly than the atrioventricular (AV) node. Automaticity is under autonomic nervous system control. Parasympathetic neurons... 

The peripheral nerves of mammals consist of bundles of neurons held together in a fibrous envelope called the epi-Murium. The change in potential for these systems is the sum of the action potentials of all the axon.s in the sy.siem if extracellular recording is attempted. Each axon in the system has a different threshold potential, and so the number of axons firing svill initially increase with increased intensity of the stimulus. Eventually, all the axon.s in the nerve will fm . and at this point, further increases in the intensity of the stimulus will cause no further increase in the size of the eciion potential. In bundles of mixed nerves, there will be multiple peaks in the action potential profile, however, because the differing types of nerve fiber will have different conduction speeds. 

Incoming signals must reach the threshold potential to trigger an action potential in a postsynaptic cell. In this example, the presynaptic neuron is generating about one action potentiai every 4 miiiiseconds. Arrivai of each action potentiai at the synapse causes a smaii change in the membrane potentiai at the axon hiiiock of the postsynaptic ceii, in this exampie a depoiarization of =5 mV. When muitipie stimuii cause the membrane of this postsynaptic ceii to become depoiarized to the threshoid potentiai, here approximateiy -40 mV, an action potentiai is induced in it. 

A postsynaptic neuron generates an action potential only when the plasma membrane at the axon hillock is depolarized to the threshold potential by the summation of small depolarizations and hyperpolarlzatlons caused by activation of multiple neuronal receptors (see Figure 7-48). 

A patient who underwent renal transplantation was given ciclosporin 6 mg/kg daily by intravenous infusion over 2 hours and intravenous meth-ylprednisolone postoperatively. He also received patient-controlled analgesia (PCA) as bolus doses of morphine 0.5 mg to a total dose of 13 mg on the first day and 11 mg on the second day. On the third day he developed insomnia, anxiety, amnesia, aphasia and severe confusion. The morphine was discontinued and the symptoms subsided after treatment with propofol, diazepam and haloperidol. It was suggested that ciclosporin may have decreased the excitation threshold of neuronal cells, which potentiated the dysphoric effects of morphine. ... 

This electric field produces action potential in excitable neuronal cells, which might result in activation of neuronal circuits when applied above certain threshold. The neuronal response depends not only on the electric field strength, but also on the pulse duration through a strength-duration curve of the form ... 

Both disodium cromoglycate and nedocromil sodium have antitussive effects in humans. In this instance, their activity occurs by increasing the depolarisation of sensory nerves, which increases the threshold for an action potential and therefore inhibits the activity of these neurons. 

An inhibitory input increases the influx of Cl to make the inside of the neuron more negative. This hyperpolarisation, the inhibitory postsynaptic potential (IPSP), takes the membrane potential further away from threshold and firing. It is the mirror-image of the EPSP and will reduce the chance of an EPSP reaching threshold voltage. 

Such clear postsynaptic potentials can be recorded intracellularly with microelectrodes in large quiescent neurons after appropriate activation but may be somewhat artificial. In practice a neuron receives a large number of excitatory and inhibitory inputs and its bombardment by mixed inputs means that its potential is continuously changing and may only move towards the threshold for depolarisation if inhibition fails or is overcome by a sudden increase in excitatory input. 

ACh can sometimes inhibit neurons by increasing K+ conductance and although it has been found to hyperpolarise thalamic neurons, which would normally reduce firing, strong depolarisation may still make the cell fire even more rapidly than normal. This appears to be because the hyperpolarisation counters the inactivation of a low-threshold Ca + current which is then activated by the depolarisation to give a burst of action potentials (McCormick and Prince 1986b). 

Na+ channels to depolarize the membrane all the way to threshold however, it brings the membrane potential closer toward it. This increases the likelihood that subsequent stimuli will continue depolarization to threshold and that an action potential will be generated by the postsynaptic neuron. 

As previously mentioned, a single action potential at a single synapse results in a graded potential only an EPSP or an IPSP. Therefore, generation of an action potential in the postsynaptic neuron requires the addition or summation of a sufficient number of excitatory inputs to depolarize this neuron to threshold. Two types of summation may occur ... 

As more EPSPs add together, the membrane depolarizes closer to threshold until an action potential is generated. Although temporal summation is illustrated in Figure 5.2 with the summation of relatively few EPSPs, in actuality, addition of up to 50 EPSPs may be necessary to reach threshold. Because a presynaptic neuron may generate up to 500 action potentials per... 

Figure 5.2 Temporal summation. Multiple excitatory postsynaptic potentials (EPSPs) produced by a single presynaptic neuron in close sequence may add together to depolarize the postsynaptic neuron to threshold and generate an action potential.

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