Sodium channels increased permeability

Sodium channels open more rapidly than K+ channels because they are more voltage sensitive and a small depolarization is sufficient to open them. Larger changes in membrane potential associated with further cell excitation are required to open the less voltage-sensitive K+ channels. Therefore, the increase in the permeability of K+ ions occurs later than that of Na+ ions. This is functionally significant because if both types of ion channels opened concurrently, the change in membrane potential that would occur due to Na+ ion influx would be cancelled out by K+ ion efflux and the action potential could not be generated. 

Very rapid-acting paralytic neurotoxin that binds to sodium channels of nerve and muscle cells depolarizing neurons by increasing the sodium channel permeability. It is obtained from South American poison-dart frogs (Phyllobates aurotaenia, Phyllobates terribilis). It is insoluble in water but soluble in hydrocarbons and other nonpolar solvents. The dried toxin can remain active for at least a year. However, it is relatively nonpersistent in the environment. 

Induction of repetitive activity in the nervous system is the principal effect of pyrethroids. Repetitive activity originates from a prolongation of the transient increase in sodium permeability of the nerve membrane associated with excitation. All pyrethroids affect sodium channel gating in a similar manner, although Type II pyrethroids are significantly more neurotoxic than Type I pyrethroids. 

A dramatic increase in Na"" permeability requires a dramatic increase in the number of channels that allow Na"" to enter the cell. Thus, the resting p is only a small frac tion of what it could be because most membrane sodium channels are closed at rest. What stimulus causes the hidden Na" channels to reveal themselves It turns out that the activation of these Na channels is triggered by membrane depolarization. When is at its usual resting levels around -70 mV, these Na" channels are closed and p is low. However, depolarization causes the channels to open. Because the voltage-activated Na channels respond to depolarization, the response of the membrane to depolarization is regenerative, and thus explosive (Figure 10.3). A small depolarization of the membrane opens Na" channels, which causes influx of Na"" into the cell and additional depolarization, which in turn opens more Na" channels. This explains the all-or-none nature of the action potential once it is triggered, it runs to completion. 

Ciguatoxin binds tightly to voltage-sensitive sodium channels. This binding leads to increased opening of sodium channels and subsequent increased cell membrane permeability to sodium. As a result, the electrical potential of involved cells is altered. 

Andromedotoxin (Grayanotoxin I) is a diterpene found in all parts of the plant. It opens sodium channels in the myocardium and increases permeability. 

Batrachotoxin is a very rapid-acting paralytic neurotoxin that increases the sodium channel permeability. 

A. Ciguatera. The toxin is produced by dinoflagellates, which are then consumed by reef fish. The mechanism of intoxication is uncertain, but may involve increased sodium permeability in sodium channels and stimulation of central or ganglionic cholinergic receptors. 

A number of substances increase the sodium permeability of excitable membranes. Their effects on sodium channels are unclear. For example, when a substance causes a permeability increase which is blocked by TTX, then it may be acting directly on the channel or indirectly on some binding site or receptor adjacent to, or some distance from, the channel. It is not easy to distinguish these possibilities in many instances. 

When superthreshold rectangular depolarizing voltage is applied to the axon, an initial wave of inward current appears as the result of the membrane s increased permeability to sodium (the opening of sodium channels). This is followed by a wave of outward current due to the conductivity of the potassium channels. Subsequently, the outward current will correspond to the ohmic conductivity of the membrane. 

Aldosterone acts on the distal tubule of the nephron to increase sodium reabsorption. The mechanism of action involves an increase in the number of sodium-permeable channels on the luminal surface of the distal tubule and an increase in the activity of the Na+-K+ ATPase pump on the basilar surface of the tubule. Sodium diffuses down its concentration gradient out of the lumen and into the tubular cells. The pump then actively removes the sodium from cells of the distal tubule and into the extracellular fluid so that it may diffuse into the surrounding capillaries and return to the circulation. Due to its osmotic effects, the retention of sodium is accompanied by the retention of water. In other words, wherever sodium goes, water follows. As a result, aldosterone is very important in regulation of blood volume and blood pressure. The retention of sodium and water expands the blood volume and, consequently, increases mean arterial pressure. 

Sir Henry Dale noticed that the different esters of choline elicited responses in isolated organ preparations which were similar to those seen following the application of either of the natural substances muscarine (from poisonous toadstools) or nicotine. This led Dale to conclude that, in the appropriate organs, acetylcholine could act on either muscarinic or nicotinic receptors. Later it was found that the effects of muscarine and nicotine could be blocked by atropine and tubocurarine, respectively. Further studies showed that these receptors differed not only in their molecular structure but also in the ways in which they brought about their physiological responses once the receptor has been stimulated by an agonist. Thus nicotinic receptors were found to be linked directly to an ion channel and their activation always caused a rapid increase in cellular permeability to sodium and potassium ions. Conversely, the responses to muscarinic receptor stimulation were slower and involved the activation of a second messenger system which was linked to the receptor by G-proteins. 

Perhaps the most well-known example is the acetylcholine receptor located on the postsynaptic membrane of the neuromuscular junction49 56 (Fig. 4-1). When bound by acetylcholine molecules, the receptor activates and opens a pore through the cell membrane, thereby increasing the permeability of the muscle cell to sodium.38 56 This action results in depolarization and excitation of the cell because of sodium influx. Another important example of a receptor-ion channel system is the gamma-aminobutyric acid (GABA)-benzodiazepine-chloride ion channel complex found on neuronal membranes in the central nervous sys-... 

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