Transient receptor potential A1 channel contributes to activation of the muscle reflex

Abstract

Koba S, Hayes SG, Sinoway LI. Transient receptor potential A1 channel contributes to activation of the muscle reflex. Am J Physiol Heart Circ Physiol 300: H201-H213, 2011. First published November 12, 2010; doi:10.1152/ajpheart.00547.2009.-This study was undertaken to elucidate the role played by transient receptor potential A1 channels (TRPA1) in activating the muscle reflex, a sympathoexcitatory drive originating in contracting muscle. First, we tested the hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate, a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle circulation. This led to a 33% increase in renal sympathetic nerve activity (RSNA). The effect of allyl isothiocyanate was a reflex because the response was prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous static contraction of the hindlimb muscles, induced by electrical stimulation of the peripheral cut ends of L4 and L5 ventral roots, increased RSNA and blood pressure. The integrated RSNA during contraction was reduced by HC-030031, a TRPA1 antagonist, injected intra-arterially (163 Ϯ 24 vs. 95 Ϯ 21 arbitrary units, before vs. after HC-030031, P Ͻ 0.05). Third, we attempted to identify potential endogenous stimulants of TRPA1, responsible for activating the muscle reflex. Increases in RSNA in response to injection into the muscle circulation of arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by-products of contraction and stimulants of muscle afferents during contraction, were reduced by HC-030031. These observations suggest that the TRPA1 located on muscle afferents is part of the muscle reflex and further support the notion that arachidonic acid metabolites, bradykinin, and diprotonated phosphate are candidates for endogenous agonists of TRPA1. muscle contraction; renal sympathetic nerve activity; thin fiber muscle afferents DURING EXERCISE, SYMPATHETIC nervous system activity is increased (33). A reflex originating in contracting skeletal muscle is considered to contribute to the sympathoexcitation seen during exercise (8,34). This muscle reflex is evoked by contraction-induced stimulation of thin-fiber muscle afferents. Group III and IV muscle afferents are stimulated by metabolic by-products, as well as by mechanical deformation of the afferent's receptive field during contraction. Afferent engagement, in turn, activates the sympathetic nervous system (19,21).Transient receptor potential (TRP) channels are a large family of related ion channels that are nonselectively permeable to cations, including calcium and magnesium (38). TRP channels are expressed widely throughout the body and are activated and regulated by a wide variety of stimuli. The TRP A1 channel (TRPA1), a member of the TRP family of ion channels, is found preferentially on nociceptive sensory neurons in mice, rats, and ...

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