Depolarization, nerve cells

Receptor interactions bupivacaine binds to the intracellular portions of sodium channels and blocks sodium influx into nerve cells which therefore prevents nerve cell depolarization. Since pain-transmitting nerve fibers tend to be thinner (small diameter) and either unmyelinated or only lightly myelinated (myelin is non-polar and lipophilic), the local anesthetic agent can diffuse more readily into them than into thicker and more heavily myelinated nerve fibers such as touch and proprioception. 

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. ... 

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. 

Rapid-acting paralytic neurotoxins that blocks transient sodium channels and inhibits depolarization of nerve cells. They are some of the causative agents of paralytic shellfish poisoning (PSP). They are obtained from dinoflagellates (Gonyaulax spp., Alexandrium spp.) and cyanobacteria (Anabaena circinalis). 

The sequence of events that result in neurotransmission of information from one nerve cell to another across the s)mapses begins with a wave of depolarization which passes down the axon and results in the opening of the voltage-sensitive calcium charmels in the axonal terminal. These charmels are frequently concentrated in areas which correspond to the active sites of neurotransmitter release. A large (up to 100 M) but brief rise in the calcium concentration within the nerve terminal triggers the movement of the synaptic vesicles, which contain the neurotransmitter, towards the synaptic membrane. By means of specific membrane-bound proteins (such as synaptobrevin from the neuronal membrane and synaptotagrin from the vesicular membrane) the vesicles fuse with the neuronal membrane and release their contents into the synaptic gap by a process of exocytosis. Once released of their contents, the vesicle membrane is reformed and recycled within the neuronal terminal. This process is completed once the vesicles have accumulated more neurotransmitter by means of an energy-dependent transporter on the vesicle membrane (Table 2.3). 

The initiation of an epileptic attack involves "pacemaker" cells these differ from other nerve cells in their unstable resting membrane potential, i.e a depolarizing membrane current persists after the action potential terminates. 

Generally, it is always only a very small part of the membrane that is depolarized during an action potential. The process can therefore be repeated again after a short refractory period, when the nerve cell is stimulated again. Conduction of the action potential on the surface of the nerve cell is based on the fact that the local increase in the membrane potential causes neighboring voltage-gated ion channels to open, so that the membrane stimulation spreads over the whole cell in the form of a depolarization wave. 

Physiological studies show that monensin is a sodium ionophore (15), that induces inotropic effect on guinea pig atria (17). The polyether toxins including ciguatoxin, okadaic acid, and the recently characterized brevetoxin (5, 16) also induce inotropic effect on guinea pig atrial tissue in vitro (17). Additionally, partially purified CTX has been implicated in the depolarization of nerve cells in vitro, which can be reversed by high concentrations of Ca tetrodotoxin and saxitoxin (18). 

It is suspected that these drugs selectively bind with the intracellular surface of sodium channels and block the entrance of sodinm ions into the cell. This leads to stoppage of the depolarization process, which is necessary for the diffusion of action potentials, elevation of the threshold of electric nerve stimulation, and thus the elimination of pain. Since the binding process of anesthetics to ion channels is reversible, the drug diffuses into the vascular system where it is metabolized, and nerve cell function is completely restored. 

The nicotinic acetylcholine receptor is a protein of 290 kD that occins in chemical synapses where conummication between nerve cells and muscle cells takes place. Binding of acetylcholine to the receptor induces opening of the ion chaimel, which is a part of the receptor. Passage of Na and ions through the receptor takes place and depolarization of the postsynaptic cell occurs. The depolarization represents a signal that-according to the nature of the postsynaptic cell—is processed in various ways. 

Action potentials are waves of depolarization and repolarization of the plasma membrane. In a resting nerve cell, the electric potential gradient (At//) across the plasma membrane is about —70 mV, inside negative. This potential difference is generated mainly by the unequal rates of diffusion of K+ and Na+ ions down concentration gradients maintained by the Na+-K+ ATPase. 

Fig. 17.3. (a) An action potential produced by a nerve-cell membrane in response to a depolarization (above the threshold) stimulus, (b) Sketch of time-dependent conductivity change of a nerve axon membrane (from Ref. 22... 

The electrostatic potential across cell membranes plays important roles in transport and in cell signaling. Muscle contraction is stimulated by depolarization of the cell membrane. Nerve cells communicate with other cells via propagated changes in membrane potential. Also the potential across membranes of intracellular organelles, such as mitochondria, can be central components of the function of the organelles. 

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