Transient Receptor Potential Vanilloid 4 Mediates Hypotonicity‐Induced Enhancement of Synaptic Transmission in Hippocampal Slices

• Published in: CNS neuroscience & therapeutics Vol. 19; no. 11; pp. 854 - 862
• Main Authors: Li, Lin, Yin, Jun, Jie, Ping‐Hui, Lu, Zi‐Hong, Zhou, Li‐Bin, Chen, Lei, Chen, Ling
• Format: Journal Article
• Language: English
• Published: Oxford Wiley-Blackwell 01.11.2013; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: AMPA receptor; Animals; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Electrodiagnosis. Electric activity recording; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; High voltage‐gated calcium channels; Hippocampus - drug effects; Hippocampus - physiology; Hypotonicity; Investigative techniques, diagnostic techniques (general aspects); Kinases; Male; Medical sciences; Mice; Mice, Inbred ICR; Morpholines - pharmacology; Nervous system; Nervous system (semeiology, syndromes); Neurology; Organ Culture Techniques; Original; Osmotic Pressure - drug effects; Osmotic Pressure - physiology; Pharmacology. Drug treatments; Proteins; Pyrroles - pharmacology; Synaptic transmission; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Toxicity: nervous system and muscle; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - physiology; TRPV4; Calcium; Central nervous system; Glutamate receptor; Encephalon; Transients; AMPA receptor; High voltage-gated calcium channels; Hypotonicity; Synaptic transmission; TRPV4; Voltage; Vanilloid receptor; Hippocampus
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.12143

Summary Aim and methods Changes in cerebrospinal fluid osmotic pressure modulate brain excitability. Transient receptor potential vanilloid 4 (TRPV4), which is sensitive to hypotonic stimulation, is expressed in hippocampus. The present study investigated the effect of hypotonic stimulation on hippocampal synaptic transmission and the role of TRPV4 in hypotonicity‐action using electrophysiological recording and pharmacological technique. Results Accompanied with the decrease in paired pulse facilitation, field excitatory postsynaptic potential (fEPSP) was enhanced by hypotonicity and TRPV4 agonist 4α‐PDD in hippocampal slices, which was sensitive to TRPV4 antagonist HC‐067047. Hypotonicity‐induced increase in fEPSP was blocked by α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist, but not N‐methyl‐d‐aspartate receptor or N‐ or P/Q‐type voltage‐gated calcium channel antagonist. High voltage‐gated calcium current (ICa) in hippocampal CA3 pyramidal neurons was not affected by hypotonicity. AMPA‐activated current (IAMPA) in hippocampal CA1 pyramidal neurons was increased by hypotonicity and 4α‐PDD, which was attenuated by HC‐067047. Inhibition of protein kinase C or protein kinase A markedly attenuated hypotonicity‐increased IAMPA, whereas antagonism of calcium/calmodulin‐dependent protein kinase II had no such effect. Conclusion TRPV4 is involved in hypotonicity‐induced enhancement of hippocampal synaptic transmission, which may be mediated through promoting presynaptic glutamate release and increasing postsynaptic AMPA receptor function.