The detection of noxious stimuli (chemical, mechanical, or thermal) occurs predominantly at the peripheral terminals of primary afferent neurons. This information is ultimately transmitted to the central nervous system to evoke appropriate protective reflexes. TRPV4 is a non selective calcium permeant, swell activated, cation channel probably involved in osmotic and mechano sensitivity. Activation by exposure to hypotonicity within the physiological range, low pH, citrate and phorbol esters exhibits an outward rectification. Once activated the channel seems to be regulated in a calmodulin dependent manner, with a negative feedback mechanism.
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