Sodium influx

In the adrenal medulla and the ganglia of parasympathetic and sympathetic nerves, the neurotransmission is mediated by acetylcholine. On the postsynaptic membranes the transmitter activates the neuronal-type of the nicotinic acetylcholine receptor. This receptor type is in fact a sodium channel, its activation leads to a sodium influx and a membrane depolarization. A pharmacological interference at the... 

Mechanism of Action An antiparasiticagent that inhibits sodium influx through nerve cell membrane channels. Therapeutic Effect Results in delayed repolarization, paralysis, and death of parasites. 

Mecfianism of Action An antiarrhythmic that decreases sodium influx during depolarization, potassium efflux during repolarization, and reduces calcium transport across the myocardial cell membrane.Decreases myocardial excitability, conduction velocity, and contractility Therapeutic Effect Suppresses arrhythmias. Pharmacokinetics Almost completely absorbed after PO administration. Protein binding 80%-90%. Metabolized in liver. Excreted in urine. Removed by hemodialysis. Half-life 6-8 hr. 

The ability to produce a concentrated urine also matures over time. In the rat, this function is not mature until 2-3 weeks after birth. This is due to the lengthening of the loops of Henle and to maturation of ion transport function. Sodium influx from the renal tubular lumen stimulates proximal tubule growth and upregulates the expression of Na+K+-ATPase, the major transporter of sodium in the kidney, in the basolateral membranes of the epithelium. 

The model nicely explained this experimental finding, but at this early stage was really no more than a working hypothesis, and was only one of a number of plausible possibilities. For example, coupling glucose influx to potassium efflux rather than sodium influx would have explained the data adequately. However, as Crane and his colleagues went on to demonstrate with a series of well designed experiments, the fundamental idea of what became known as the Crane hypothesis remained plausible while other obvious hypotheses were excluded (Crane, 1975). 

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-... 

Because sodium influx plays an important role during action potential generation during phase 0 of... 

General anesthetics alter the excitation of the neuronal membrane and modify impulse conduction. Specifically, the general anesthetics have the following common properties (1) They decrease the activity of neurons by increasing their threshold to fire, and (2) they prevent the action potential from rising to a normal rate by interfering with sodium influx (Figure 65.7). 

Na+/K+ ATPase, by removing intracellular sodium, is the major determinant of sodium concentration in the cell. The sodium influx through voltage-gated channels, which occurs as a normal part of almost all cardiac action potentials, is another determinant. As described below, Na+/K+ ATPase appears to be the primary target of cardiac glycosides. 

A medium throughput approach to evaluating sodium channel activity is the measurement of sodium flux across cell membranes [103]. In these experiments, a tracer that permeates the channel and is easily quantifiable is used to analyze sodium influx. Traditionally, radioactive tracers such as 22Na+ or [14C]guanidinium have been used. Alternatively, Li+ can be used as a tracer and analyzed by atomic absorption spectrometry. Sodium flux assays can be used to test approximately 105 compounds per year. They offer a robust readout of channel activity, but lack voltage control and temporal resolution. To examine sodium channel blockade by measuring sodium flux,... 

Mechanism of action Quinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0 (Figure 17.6). It also decreases the slope of Phase 4 spontaneous depolarization. 

Energy for transport by pumps may be derived from ATP hydrolysis or from the ionic gradients of another ion. This is the case of the sodium/calcium exchanger, which uses the electrical energy stored in the sodium gradient across the plasma membrane to transport calcium out of the cell while harnessing the energy from concerted sodium influx (Komuro et al, 1992). 

Immediately after the onset of focal brain ischemia, oxygen and glucose deprivation result in loss of adenosine triphosphate (ATP), loss of maintenance of normal ion channels and neuronal depolarization (Wahlgren and Ahmed, 2004) as evidenced by calcium and sodium influx into the cells. 

Name the membrane valves that open and close for potassium efflux and sodium influx. 

Studies in rat alveolar type II cells have demonstrated that terbutaline stimulates sodium influx as well as potassium and chloride release via cAMP accumulation. 

Suppresses sodium influx by binding to the sodium channel, prolonging the sodium channel s inactivation, and preventing neurons from firing... 

With a single channel conductance of more than 100 pS,1,20,22 only ten hemichannels need to be open to produce a millimolar cellular sodium influx,83 and such a millimolar increase in the intracellular sodium concentration has been measured during ischemia in whole hearts.84-86 The osmotic imbalance resulting from increased AMP, inorganic phosphate and sodium concentrations results in swelling and finally membrane rupture of the ischemic cells. 

Dargent B, Couraud F 1990 Down-regulation of voltage-dependent sodium channels initiated by sodium influx in developing neurons. Proc Natl Acad Sci USA 87 5907-5911... 

Not all cells in the cardiac conduction system rely on sodium influx for initial depolarization. Some tissues depolarize in response to a slower inward ionic current caused by calcium influx. These calcium-dependent tissues are found primarily in the SA and AV nodes (both L- and T-channels) and possess distinct conduction properties in comparison with the sodium-dependent fibers. Calcium-dependent cells generally have a less negative RMP (-40 to -60 mV) and a slower conduction velocity. Furthermore, in calcium-dependent tissues, recovery of excitability outlasts full repolarization, whereas in sodium-dependent tissues, recovery is prompt after repolarization. These two types of electrical fibers also differ dramatically in how drugs modify their conduction properties (see below). 

Triggered automaticity is also a possible mechanism for abnormal impulse generation. Briefly, triggered automaticity refers to transient membrane depolarizations that occur during repolarization (early after-depolarizations [EADs]) or after repolarization (delayed afterdepolarizations [DADs]) but prior to phase 4 of the action potential. After-depolarizations may be related to abnormal calcium and sodium influx during or just after full cellular repolarization. Experimentally, early after-depolarizations may be precipitated by hypokalemia, type la antiarrhythmic drugs, or slow stimulation rates— any factor that blocks the ion channels (e.g., potassium) responsible... 

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