Low external NaCl concentration and low osmolarity enhance voltage-gated Ca currents but depress K currents in freshly isolated rat hippocampal neurons.
In previous experiments, reducing bath osmolarity (pi o) or external NaCl concentration ([NaCl]o) caused an increase in synaptic currents recorded in whole-cell configuration from pyramidal cells of CA1 region of hippocampal slices. Slow inward current surges, assumed to be calcium currents, were also enhanced. This contrasted with the strong, reversible, generalized depression of voltage-dependent ion currents in isolated neurons, caused by sudden, brief exposure to very low pi o. I have now recorded voltage-dependent whole-cell Na-, K- and Ca-currents from freshly isolated hippocampal CA1 pyramidal neurons during more gradual lowering of pi o or [NaCl]o. Changes in cell size were determined from image areas and changes in intracellular Ca2+ activity were measured as the ratio of the fluorescences of fluo-3/fura-red by confocal microscopy. Iso-osmotic substitution of 40 or 60 mM NaCl by mannitol or sucrose for 5-7 min, or reducing pi o by deleting NaCl from the bath (osmolarity decreased by 69 or 108 mosM/kg) depressed K currents. Na currents were also strongly depressed, but this is in part attributable to reduced driving potential and ionic conductance. The depression of IK varied widely and it was inversely correlated with the degree of hypotonic swelling, suggesting that reduced ion channel conductance also reduces permeability to water. Reducing [NaCl]o by 60 mM, or pi o by 105 mosM/kg consistently and reversibly increased Ca currents. Intracellular Ca2+ level also increased, but the changes of [Ca2+]i and ICa were not correlated. Facilitation of the Ca influx into presynaptic terminals could explain the increase of synaptic currents. Depression of outward currents could also contribute to the irritability of the central nervous system typical of clinical hyponatremia.
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