Effects of hypertonia on voltage-gated ion currents in freshly isolated hippocampal neurons, and on synaptic currents in neurons in hippocampal slices.
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 (pi(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 Ca2+ current shifted to a more negative potential, suggesting stronger depression of high- compared to low-voltage activated currents. During 30 min high pi(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 pi(o) is not selective, but the degree of the suppression varies among current types. Raising pi(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.
Huang
R
R
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Somjen
G G
GG
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006982:Hypertonic Solutions / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D015220:Calcium Channels; D006982:Hypertonic Solutions; D007473:Ion Channels; D015221:Potassium Channels