Effects of hypertonia on voltage-gated ion currents in freshly isolated hippocampal neurons, and on synaptic currents in neurons in hippocampal slices

Abstract

We studied the effects of hypertonia on voltage-gated currents of freshly isolated hippocampal CA1 neurons, using open pipette whole-cell as well as gramicidin-perforated patch-clamp recording. Extracellular osmolarity ( π o) was raised by adding mannitol (50 or 100 mmol/l) to the bathing solution. Hypertonia depressed voltage-gated sodium, potassium and calcium currents in all trials. The threshold activation voltage of the currents did not change during hypertonic depression, but maximal activation of Ca 2+ current shifted to a more negative potential, suggesting stronger depression of high- compared to low-voltage activated currents. During 30 min high π o treatment (recorded with open pipette), the depression reached maximum in 10–15 min of exposure. The depression of the computed transient component of the K + current recorded by open pipette was statistically not significant. Following hypertonic treatment recovery of the I Na, the sustained I K and sustained I Ca were incomplete compared to control cells maintained in normal solution for an equal length of time. In hippocampal tissue slices hypertonia (+25, +50 and +100 mmol/l fructose) reversibly depressed excitatory postsynaptic currents (EPSCs). We conclude that the shutdown of membrane ion currents by elevated π o is not selective, but the degree of the suppression varies among current types. Raising π o in human patients, possibly combined with mild artificial acidosis, may be useful in the prevention and treatment of acute crises associated with excessive excitation or depolarization of neurons.