Action potential-independent release of glutamate by Ca2+ entry through presynaptic P2X receptors elicits postsynaptic firing in the brainstem autonomic network.

P2X receptors are ATP-gated channels permeable to cations including Ca(2+). In acute slices containing the nucleus of the solitary tract, in which neuronal ATP release and ATP-elicited physiological responses are demonstrated in vivo, we recorded spontaneous action potential-independent EPSCs [miniature EPSCs (mEPSCs)]. Activation of presynaptic P2X receptors with alpha,beta-methylene ATP (alphabetamATP) triggered Ca(2+)-dependent glutamate release that was resistant to blockade of voltage-dependent calcium channels but abolished by P2X receptor antagonists. mEPSCs elicited with alphabetamATP were of larger amplitude than basal mEPSCs and resulted in postsynaptic firing caused by temporal summation of miniature events. The large-amplitude mEPSCs provoked by alphabetamATP were likely to result from highly synchronized multivesicular release of glutamate at single release sites. Neither alphabetamATP nor ATP facilitated GABA release. We conclude that this facilitated release and consequent postsynaptic firing underlie the profound autonomic responses to activation of P2X receptors observed in vivo.