A role for TRP channels in carotid body chemotransduction?

Abstract

The hypoxia-induced inhibition of type I cell, K channels leads to membrane potential depolarization and subsequent calcium entry and neurosecretion. Whilst the precise nature of the K channel involved in this transduction mechanism is disputed, a role for voltage gated calcium entry is largely accepted. Recently, however, the identification and location of TRP channels have been revealed in the carotid body type I cell by immunostaining, The TRP channel family mediates calcium entry in a wide variety of tissues and cells in response to G-protein activation. In a previous study, we found that whilst calcium free + EGTA perfusate could abolish the carotid body chemoafferent response to hypoxia, nifedipine, as an antagonist for L-type calcium channels, only blocked 45% of the response, suggesting multiple routes for calcium entry. In this study, we found that 2-APB, a common antagonist for TRP channels, effectively reversed the hypoxia/hypercapnia induced rat carotid body chemoaffarent discharge in vitro, demonstrating a potential role of TRP channel in carotid body chemosensing. We thereafter, utilized EGTA to deplete internal calcium stores, and found this induced a significant increase in discharge frequency. This discharge was less sensitive to nifedipine but was prevented by pre incubating the carotid body with 2-APB. In a separate study, we have demonstrated that polyunsaturated fatty acids, eg arachidonic acid (AA), can directly inhibit TRPC3 and consistent with this, we found that AA could effectively decrease the chemoafferent discharge caused by hypoxia/hypercapnia and EGTA. This work was supported by The British Heart Foundation