Na+ ion channel

Drugs that block the nicotinic receptors on autonomic ganglia, such as hexamethonium, probably do so by actually blocking the Na+ ion channel rather than the receptor. Generally these receptors appear to resemble the central ones more than those at the neuromuscular junction and dihydro-jS-erythroidine is one drug that it is an effective antagonist in both ganglia and the CNS. 

Sodium ions A marked and rapid increase in the Na ion transport across the plasma membrane into a nerve or muscle cell, via the Na ion channel, causes a depolarisation of the membrane that initiates a transient flux of electrical activity along the nerve or muscle (that is, an action potential) (Chapters 13 and 14). 

Receptors are located on non-motile cilia that project from the dendrite of the neurone into the mucus layer. It is the cilia that possess the receptor for the pheromone and respond to it via an effector system that results in opening of a Na" ion channel. This depolarises the membrane across the sensory cell which, if of sufficient magnitude, leads to generation of action potential along the axon with which it forms a synapse. The effector system is adenyl cyclase and the generation of cyclic AMP, a process that involves the G-protein (Figure 12.15). 

The cyclase produces cAMP which results in opening of a Na" ion channel in the membrane of the sensory cell. If a sufficient number of Na " ions enter, this depolarises the membrane and initiates an action potential along the axon to the olfactory nerve. Further effects depend upon interaction between the nerves and synapses within the olfactory centre in the brain. This can result in physiological effects in other parts of the body which define the function of the pheromone. The effects of pheromones on the sexual responses of men and women are discussed in Chapter 19 (see Figure 19.17). 

Figure 12.15 Effectx)r mechanism for a pheromone. The mechanism is similar to that shown in Figure 12.6 except cyclic AMP leads to opening of a Na ion channel which will result in depolarisation and initiation of an action potential. It is of interest that the physiology/biochemistry is opposite to that involved in the detection of light, in which the signalling system results in hyperpolarisation of a nerve ratfer that hypopolarisation (Chapter 15 see Figure 15.10).

The concentration of Na ions is greater on the outside of the neurone than on the inside but the Na ion channel is closed in the resting state. 

Depolarisation results in the opening of further Na ion channels in the membrane. 

Propagation of the action potential along the axon occurs because the voltage change opens the Na ion channels ahead, i.e. the channels are voltage gated (Figure 14.5 see Box 14.1). 

Immediately after the passage of an action potential, the Na ion channels close spontaneously and cannot be re-opened for a period of time. This is the refractory period. An action potential therefore cannot proceed in the opposite direction, i.e. it is unidirectional, which imposes a direction on propagation of the whole action potential. This is analogous to the means by which directionality is achieved in a metabolic pathway or a signalling sequence of reactions within either process there is at least one irreversible (non-equilibrium) reaction which provides directionality (Chapter 2). 

Channel-forming proteins exhibit a number of structural motifs the influenza virus M2 proton channel and voltage-gated channels for K+, Na+ and Ca2+are all composed of four identical subunits that aggregate to form a central pore as shown in Fig. 5.7 an acid sensing Na+ ion channel has a similar structure but with threefold symmetry Ca2+ release channels, the divalent metal ion transporter CorA, the... 

Sulfogalactosylceramide (Sulfatide) synthesis and degradation in CNS and PNS. Regional and cellular abnormalities may also be related to defects in the synthesis of sulfatides. Sulfatides, coded by the galactosylceramide sulfotransferase gene, are essential for maintenance of Na" ion channels on myelinated axons but are not required for initial clusto formation (Ishibashi et al., 2002). Mice deficient for this gene are unable to synthesize sulfatides. They display abnormal paranodal junctions in the CNS and PNS, whereas their compact myelin is preserved (Honke et al.,... 

The highest density of Na ion channels oteurs at the nodes of Ranvier. The myelinated intcmodal sections of the neuron contain far fewer Na channels. In addition, these intemodal regions arc electrically insulated and so do not contribute to the action potential. Consequently, the potential produced at the nodes of Ranvier must be strong enough to produce an effect up to I mm away. 

The restricted pattern of SCNSA is novel and contrasts with the more diffuse expression of other Na ion channel al subunits (Felts et al 1997, Whitaker et al 2000), predicting a specific but as yet undetermined role in regulating excitability and synchronization within these circuits. This uneven spatial distribution pattern of Na+ channel al subunit expression, mirrors a similar range of expression patterns of al subunits for voltage-gated Ca- channels. 

Blocks axonal Na+ ion channels in their inactivated state (state or rate -dependent blockade) and results in decreased SHFRF. Also used as antiarrhythmic and backup in bipolar disorder. 

Answer B. Back to Basic Principles and the Henderson-Hasselbalch relationship. From the table, pH - pKa = -2.2. For a weak base, a value of -2 represents 1% nonionized, so in the present case the percentage of the local anesthetic in the nonionized form is <1%. Local anesthetics usually have reduced activity when injected into tissue that is septic because only a small fraction of the molecules are in the form capable of crossing biomembranes. Remember that this is not the form that interacts with the Na ion channel—that s the ionized form of the local anesthetic. 

C) Phenobarbital has multiple actions, including enhancement of the effects of GABA, antagonism of glutamate receptors, and blockade of Na+ ion channels... 

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