The nerve endings of type I units make synapse-like contacts with Merkel cells in the basal epidermis of the skin. Recent work demonstrated the existence of vesicular glutamate transporters in Merkel cells (Hitchcock et al. 2004), and metabotropic glutamate (mGlu) receptors on Merkel cells and associated nerve terminals (Tachibana et al. 2003). It is therefore possible that these receptors play a modulatory role in neurotransmission at this junction. We examined the effects of two different mGlu receptor antagonists on the evoked responses of type I units. Whisker pads were taken from nine humanely killed adult male Wistar-derived rats. Extracellular single unit recordings were made from sinus hair slowly adapting mechanoreceptor units using methods previously described (Fagan & Cahusac, 2001). The vibrissa hair shaft was deflected mechanically for 5 s (0.5 s onset and offset ramps, 4 s plateau). The preparation was superfused with oxygenated synthetic interstitial fluid, by which drugs could be administered. Means±S.D. are given. During the application of broad spectrum mGlu receptor antagonist LY341495 (10 – 100μM) the static component of the response was significantly increased to 119-162% of control (t(4) = 4.95, p = 0.008). The dynamic response component was more variable and generally less affected (95-194% of control, t(4) = 2.009, p = 0.104). The effect on spontaneous firing was highly variable, although an increase was often seen (mean firing before drug was 1.3±1.7 Hz, mean during drug was 3.5±4.4 Hz). The effects were relatively short lasting after wash; mean duration was 19±14 min. The more selective mGlu receptor antagonist (RS)-4C3HPG (10 – 100μM) was also tested. Again, the static component was significantly affected (86-207% of control, t(4) = 3.051, p = 0.038), while the dynamic was less so (94-133% of control, t(4) = 2.29, p = 0.084). Spontaneous firing, although variable, tended to increase during the drug application (before, 0.9±1.0 Hz; during drug, 3.1±4.2 Hz). The mean duration of the effects was 34±25 min. The effects observed were clearly dose-dependent. Slowly adapting type II units were studied as a control, since lanceolate endings do not make synaptic contacts. In two units using LY341495 (10μM) there was no apparent effect (static = 101%, dynamic = 108% of control). A further two units using (RS)-4C3HPG (100μM), was again without effect (static = 97%, dynamic = 97% of control). These experiments show that mGlu receptor antagonists selectively increase responses of type I units. The concentrations of LY341495 used were sufficient to block all known types of mGlu receptors. In contrast the concentrations of (RS)-4C3HPG used were only sufficient to block mGlu1 receptors (Kingston et al. 1995). The results suggest that Group I mGlu receptors modulate either neurotransmission or excitability at the Merkel-neurite junction.
University of Bristol (2005) J Physiol 567P, C41
Oral Communications: Blockade of metabotropic glutamate receptors enhances responses of rat slowly adapting type I cutaneous mechanoreceptors in vitro
Cahusac, Peter M.B.; Senok, Solomon S.;
1. Department of Psychology, University of Stirling, Stirling, United Kingdom. 2. Department of Physiology, Arabian Gulf University, Manama, Bahrain.
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Where applicable, experiments conform with Society ethical requirements.