Endogenous activation of neurokinin‐1 receptor (NK1R) expressing ventral respiratory group (VRG) neurons by somatic afferent stimulation

Abstract

Previous work from our laboratory has demonstrated that: 1) exogenous activation of NK1Rs increased the firing rate of functionally-identified VRG neurons (Fong and Potts, 2004); and 2) somatic afferent stimulation excited augmenting expiratory neurons (Eaug, Potts et al., 2005). The aim of the current study was to examine the role of endogenous activation of NK1Rs on inspiratory- (I) and expiratory-(E) related VRG neurons. Using the in situ arterially-perfused rat preparation, we used multibarrel microelectrodes to record extracellular activity from 32 VRG neurons during electrically-evoked muscle contraction. Muscle contraction inhibited I (6/12) and post-inspiration (post-I, 7/7) neurons when the stimulus was delivered during its normal firing phase. In contrast, the firing rate of Eaug (5/6) and pre-inspiratory (Pre-I, 3/5) neurons was increased when somatic stimulation was delivered during late-expiration (E2 phase). To determine whether contraction-evoked changes in firing rate of VRG neurons was mediated by endogenous release of substance P, the NK1R antagonist CP99,994 (10mM) was picoejected onto 13 of 32 VRG neurons. NK1R blockade had no effect on contraction-evoked inhibition of I (3/3) or post-I (4/4) neurons. However, CP99,994 attenuated contraction-induced excitation of E2 (2/3) by 60% and Pre-I (2/3) by 50 percent. NK1R blockade reduced basal firing rate in only 1 of 6 neurons. These data suggest that endogenous activation of NK1R by contraction-sensitive somatic afferents modulates the excitability of E2 and Pre-I neurons. This work was supported by NIH grant HL059167 (JTP).