Nerve depolarization

Kotlikoff Would your prediction be that at the end of an agonist response or nerve depolarization, at its termination you would get CCE, and presumably some large spark of Ca2+ ... 

A directly proportional correlation has been reported [28] between 5-HT3 binding and inhibition of 5-HT-induced nerve depolarization with selected compounds BRL 43594, GR 65630, GR 38032F, quipazine, ICS 205-530, MDL 72222 and metoclopramide (listed in order of decreasing potency). Thus, a linkage between functional and receptor affinity has been established in vitro. 

Local anesthetics produce anesthesia by blocking nerve impulse conduction in sensory, as well as motor nerve, fibers. Nerve impulses are initiated by membrane depolarization, effected by the opening of a sodium ion channel and an influx of sodium ions. Local anesthetics act by inhibiting the channel s opening they bind to a receptor located in the channel s interior. The degree of blockage on an isolated nerve depends not only on the amount of dmg, but also on the rate of nerve stimulation (153—156). 

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. 

Voluntary muscle contraction is initiated in the brain-eliciting action potentials which are transmitted via motor nerves to the neuromuscular junction where acetylcholine is released causing a depolarization of the muscle cell membrane. An action potential is formed which is spread over the surface membrane and into the transverse (T) tubular system. The action potential in the T-tubular system triggers Ca " release from the sarcoplasmic reticulum (SR) into the myoplasm where Ca " binds to troponin C and activates actin. This results in crossbridge formation between actin and myosin and muscle contraction. 

The membranes of nerve cells contain well-studied ion channels that are responsible for the action potentials generated across the membrane. The activity of some of these channels is controlled by neurotransmitters hence, channel activity can be regulated. One ion can regulate the activity of the channel of another ion. For example, a decrease of Ca + concentration in the extracellular fluid increases membrane permeability and increases the diffusion of Na+. This depolarizes the membrane and triggers nerve discharge, which may explain the numbness, tinghng, and muscle cramps symptomatic of a low level of plasma Ca. ... 

When large areas of the membrane are depolarized in this manner, the electrochemical disturbance propagates in wave-like form down the membrane, generating a nerve impulse. Myelin sheets, formed by Schwann cells, wrap around nerve fibers and provide an electrical insulator that surrounds most of the nerve and greatly speeds up the propagation of the wave (signal) by allowing ions to flow in and out of the membrane... 

Figure 49-8. Diagram of the relationships among the sarcolemma (plasma membrane), a T tubule, and two cisternae of the sarcoplasmic reticulum of skeletal muscle (not to scale). The T tubule extends inward from the sarcolemma. A wave of depolarization, initiated by a nerve impulse, is transmitted from the sarcolemma down the T tubule. It is then conveyed to the Ca release channel (ryanodine receptor), perhaps by interaction between it and the dihydropyridine receptor (slow Ca voltage channel), which are shown in close proximity. Release of Ca from the Ca release channel into the cytosol initiates contraction. Subsequently, Ca is pumped back into the cisternae of the sarcoplasmic reticulum by the Ca ATPase (Ca pump) and stored there, in part bound to calsequestrin.

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... 

CTx that has been purified from muscles of Gymnothorax javanicus stimulates the release of neurotransmitters such as 7-aminobutyric acid and dopamine from rat brain nerve terminals. It causes a membrane depolarization of mouse neuroblastoma cells and, under appropriate conditions, it creates spontaneous oscillations of... 

In squid giant axons, PbTx causes a depolarization of the plasma membrane, repetitive discharges followed by depression of action potentials, and a complete blockade of excitability. This action is antagonized by TTX (83,84). PbTx depolarizes nerve terminals and induces neurotransmitter release (85,86) it depolarizes skeletal muscle cells (87) and increases the frequency of action potentials in crayfish nerve cord (88). PbTx also produces a contraction of the guinea pig ileum (89). All these effects are prevented by TTX. 

Suberitine, a small protein from the sponge Suberites domcuncula, has a variety of actions. It is not very toxic but causes hemolysis in human erythrocytes, flaccid paralysis in crabs and depolarization of squid axon and abdominal nerve of crayfish. A variety of extracts from Porifera have been shown to be toxic to fish and generally have cytotoxic and hemolytic actions (62,63). As discussed previously, a variety of sponges exude substances that are toxic to fish. 

The AChR is composed of five subunits, ql2Pi - A neurotoxin attaches to the a subunit. Since there are 2 mol of the a subunits, 2 mol of neurotoxins attach to 1 mol of AChR. A neurotransmitter, acetylcholine (ACh), also attaches to the a subunit. When the ACh attaches to the AChR, the AChR changes conformation, opening up the transmembrane pore so that cations (Na" ", K ) can pass through. By this mechanism the depolarization wave from a nerve is now conveyed to a muscle. The difference between neurotoxin and ACh is that the former s attachment does not open the transmembrane pore. As a consequence, the nerve impulse from a nerve cannot be transmitted through the postsynaptic site (27). 

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