Glycine activates myenteric neurones in adult guinea-pigs

1. We studied the effects of glycine on myenteric neurones and muscle activ ity in the colon and stomach of adult guinea-pigs. 2. Intracellular recordings revealed that myenteric neurones responded to l ocal microejection of glycine (1 mM) with a fast, transient membrane potent ial depolarisation (57 % of 191 colonic neurones and 26 % of 50 gastric neu rones). Most glycine-sensitive neurones had ascending projections and were choline acetyltransferase immunoreactive. Glycine preferentially activated neurones with a late afterhyperpolarisation (AH-neurones) and tonic spiking neurones with fast synaptic inputs (tonic S-neurones) but less frequently phasic 8-neurones and inexcitable (non-spiking) neurones. The depolarisatio n had a reversal potential at -19 +/- 13 mV, which was increased by 18 +/- 10 % upon lowering extracellular chloride concentration and decreased by 38 +/- 14 % in furosemide (frusemide, 2 mM). 3. Strychnine (300 nM) reversibly abolished the glycine-induced depolarisat ion and the Cl- channel blocker picrotoxin (100 muM) reduced the amplitude of the depolarisation by 55 +/- 6 %. The glycine effect was a postsynaptic response because it was not changed after nerve blockade with tetrodotoxin (1 pi) or blockade of synaptic transmission in reduced extracellular [Ca2+] . The effect was specific since the response was not changed by the nicotin ic antagonists hexamethonium (200 mum) and mecamylamine (100 mum), the GABA (A) receptor antagonist bicuculline (10 muM), the NMDA antagonist MK-801 (2 0 muM) or the 5-HT3 antagonist ICS 205930 (1 muM). 4. Glycine (1 mM) induced a tetrodotoxin- and strychnine-sensitive contract ile response in the colon; the contractile response in the stomach was tetr odotoxin insensitive. 5. Glycine, activated myenteric neurones in the adult enteric: nervous syst em through strychnine-sensitive mechanisms. The glycine-evoked depolarisati on was caused by Cl- efflux and the maintenance of relatively high intracel lular chloride concentrations involved furosemide-sensitive cation-chloride co-transporters.