Hypertonic stimulation inhibits synaptic transmission in hippocampal slices through decreasing pre-synaptic voltage-gated calcium current

Acute changes in the cerebrospinal fluid osmotic pressure modulate the brain excitability. The present study investigated the effect of hypertonic stimulation on the synaptic transmission in hippocampal slices. It was found that the slope of excitatory postsynaptic potential (EPSP) in hippocampal CA1 area was inhibited after the hypertonic treatment. Accompanied with the inhibition in EPSP slope, the paired-pulse facilitation (PPF) was increased by hypertonicity. Transient receptor potential vanilloid 4 (TRPV4 receptor) antagonists did not block hypertonicity-action. High voltage-gated calcium current (IHVA) in hippocampal CA3 neurons was decreased by hypertonicity, whereas the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-induced current in hippocampal CA1 neurons was unaffected. Additionally, inhibition of phosphatidylinositol 3-kinase (PI3K) or protein kinase A (PKA) markedly attenuated hypertonicity-induced decrease of IHVA, whereas antagonism of phosphorylated ERK1/2 mitogen-activated protein kinase (pERK1/2) had no effect. We conclude that hypertonic stimulation inhibits synaptic transmission in hippocampal slices through decreasing pre-synaptic voltage-gated calcium current.

► Hypertonicity inhibits the synaptic transmission in hippocampal slices.
► Hypertonicity decreases high voltage-gated calcium current in hippocampal CA3 neuron.
► PI3K and PKA signal systems mediate hypertonic-action on calcium current.
► The AMPA-induced current in hippocampal CA1 neuron is unaffected by hypertonicity.
► Hypertonicity decreases pre-synaptic calcium current to inhibit synaptic transmission.