Mechanotransduction by intraganglionic laminar endings of vagal tension receptors in the guinea-pig oesophagus

Abstract

Vagal mechanoreceptors to the guinea-pig oesophagus, recorded extracellularly, in vitro, fired spontaneously at 3.3± 0.2 Hz, (n = 75, from 57 animals), and had low thresholds to circumferential stretch. In this study, we have investigated whether mechanotransduction by intraganglionic laminar endings (IGLEs)directly relies on mechano-gated ion channels, or whether it is due to chemical activation by neurotransmitters (glutamate or ATP)released from other cells during mechanical distortion. Rapid distortion of focal transduction sites (IGLEs) evoked action potentials with a latency of < 10 ms. Antagonists to ionotropic (AP5, memantine and 6,7-dinitroquinoxaline-2,3-dione (DNQX)) and metabotropic glutamate receptors (N-phenyl-7-(hydroxyimino)cyclo-propa[b]chromen-la-carboxamide (PHCCC) and (RS)-a-methyl-4-phosphono-phenylglycine (MPPG)) did not affect mechano-transduction. Glutamate, NMDA and the selective mGluR group II and III agonists, (2R, 4R)-APDC and L-AP4, had no effect on spontaneous or stretch-induced firing. The P2X purinoreceptor agonist, α,β-methylene ATP, caused concentration-dependent excitation of vagal mechanoreceptors (EC50= 22.2 μM) which was blocked by the non-selective P2 antagonist PPADS (30 μM). On its own, PPADS affected neither stretch-induced firing nor spontaneous firing. Neither Ca2+-free solution (1 mM EDTA, 3.6 mm Mg2+ solution nor Cd2+ (100 μm) blocked stretch-induced firing. Thus chemical transmission is not involved in activation of vagal mechanoreceptors. The blocker of stretch-activated channels, Gd3+ (300 μM), did not inhibit stretch-induced firing. However, benzamil (100 μM) significantly inhibited spontaneous and distension-evoked firing in a stretch-dependent manner; proportionally greater inhibition was seen with larger stretches. The results suggest that IGLEs of vagal tension receptors directly transduce mechanical stimuli probably via benzamil-sensitive, Gd3+-insensitive, stretch-activated ion channels, and that chemical transmission is not involved in transduction.