Hyponatremia propitiates and increases susceptibility to seizure episodes. In vitro, hyposmolarity induces hyperexcitability and epileptiform activity and increases the amplitude of excitatory postsynaptic potentials. Synaptic (increased glutamate vesicular release) and non-synaptic (swelling-induced extracellular space shrinkage and ephaptic interactions) might be responsible for the hyposmolarity effects on brain excitability. Neuronal volume constancy in hyponatremia is preserved by the isovolumetric regulation, relying importantly on organic osmolytes. Changes in cell volume are closely linked to neuronal death: swelling characterizes necrotic death as in acute ischemic episodes or brain trauma, whereas volume decrease is typical of apoptotic death. Swelling in necrotic death results from the intracellular Na+ increase followed by Cl- and water influx. Na+ accumulation is due initially to the Na+/K+ ATPase dysfunction and subsequently from the Na+ influx through the overactivated ionotropic glutamate receptors. A second wave of swelling generates by excitotoxic derived formation of reactive oxygen species, membrane lipoperoxidation and further ion overload. Excessive swelling contributes to membrane rupture and release of cell debris, propagating the damage to adjacent cells. Apoptotic death is characterized by cell volume decrease termed apoptotic volume decrease, which in neurons seems to occur by mechanisms remarkably similar to those operating in the hyposmotic swelling-activated volume regulatory decrease, i.e. channel-mediated efflux of K+ and Cl-. A variety of K+ channels and the volume-regulated anion channel participate in apoptotic volume decrease. K+ has a protagome role as an early element in neuronal apoptosis since a delayed rectifier K+ current IKDR is enhanced by apoptosis prior to the caspase activation, increased extracellular K+ and IKDR blockers attenuate apoptosis and intracellular K+ loss through ionophores induces apoptosis. Volume-regulated anion channel participates as well in the Cl- efflux. although its role and hierarchy in the apoptotic program are not well defined. Efflux of organic osmolytes, such as taurine participate as well in apoptotic volume decrease.
Última actualización: 11/12/2017