Sodium - Biological Effects
Physiological role
Because of its high concentration, sodium takes part in the establishment of the plasma osmolality which is 300 mOsm/L approximately.
Sodium plays the essential part in the cellular depolarization of excitable tissues, nerve and muscle. It penetrates into the cells by voltage-gated channels and receptor-dependant channels and is extruded by the Na+/K+ -ATPase pump. These transfers are important for their consequences, but involve a very low quantity of sodium and do not influence the sodium concentration in the extracellular medium.
The sodium gradient created by the Na+/K+ -ATPase pump allows exchanges of ions and cotransportion of substrates (glucose, serotonin…).
Sodium and potassium modulate, probably allosterically, the activity of certain enzymes.
Pharmacological consequences
Many drugs are involved directly or indirectly in the transfer of sodium.
- Drugs and messengers modulating the opening of the cation receptor-channels and consequently sodium and possibly calcium transfer:
- Inducing opening:
- Acetylcholine, as agonist of nicotinic receptors.
- Serotonine, as agonist of 5HT3 receptors.
- Glutamate, as agonist of NMDA receptors.
- Inhibiting opening:
- neuromuscular blocking agents
- 5HT3 antagonists used as antiemetic agents
- NMDA antagonists.
- Drugs modulating the opening of voltage-gated sodium channels :
- Openers : sodium-channel openers
Ibutilide is an antiarrhythmic which lengthens phases 1 and 2 of the cardiac action potential by prolonging the time during which the slow sodium channels are open. In addition it slows the efflux of potassium.
The “openers” of sodium channels, active at the level of the myocardium, could have a digoxin-like effect, i.e. an inotrope cardiac effect because the rise in the concentration of intracellular sodium can activate the Na + / Ca 2+ exchanger and increase the intracellular calcium concentration indirectly.
Certain insecticides prolong the opening of the voltage-gated sodium channels
- Inhibitors of opening: sodium-channel inhibitors
Dugs which inhibit the opening of voltage-dependant sodium channels increase the polarization of the cell and decrease its excitability. They are called voltage-gated sodium channel inhibitors: local anesthetics, antiepileptic drugs and class I antiarrhythmics (see below)
- Drugs inhibiting Na+/K+ -ATPase pump:
Digoxin inhibits the Na+/K+ -ATPase pump and is a cardiac inotrope.
- Drugs inhibiting the sodium-dependant cotransports:
Many drugs inhibit the sodium-dependant cotransports, such as those which are involved in the reuptake of biogenic amines, norepinephrine and serotonin, and have an antidepressant effect.
- Diuretics:
Diuretics by increasing the renal sodium elimination, reduce its amount in the body
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