Bulbar respiratory neurons of unanesthetized, decerebrate cats were impaled with the center pipette of a compound, coaxial microelectrode. This electrode allowed intracellular recording of membrane potential (MP) through the central pipette and extracellular iontophoresis of glycine or gamma-aminobutyric acid (GABA) from micropipettes encircling the center pipette with their tips recessed 20-40 microns from the tip of the center pipette. 2. Seventy-seven studies were carried out on 32 inspiratory and 28 postinspiratory neurons with the use of brief pulses (0.3-0.5 s) or long pulses (3-10 s) spanning one or more respiratory cycles. In both neuronal types, GABA and glycine decreased spike frequency, synaptic "noise," respiratory fluctuations of MP, and "input" resistance in a dose-related fashion. 3. In most cases, the membrane was hyperpolarized by the amino acid. The reverse response (depolarization) was observed when the membrane had been hyperpolarized by current clamp. This reversal from hyperpolarization to depolarization occurred at a MP of -81 +/- 2.3 mV (mean +/- SE, n = 7) for glycine and -81 +/- 1.6 (n = 6) for GABA. 4. After intracellular iontophoresis of chloride ions, application of GABA and glycine depolarized the membrane. 5. During relatively long (3-10 s) periods of iontophoresis of glycine or GABA, the effects on MP and input resistance waned. In some cases (23%), the amino acid depolarized the membrane at the most hyperpolarizated portion of the MP trajectory. This was never observed with brief iontophoretic pulses. Such effects of long duration iontophoresis may reflect changes in membrane properties secondary to the primary action of the amino acid on the membrane of the impaled neuron or indirect synaptic actions via changes in discharge of neighboring neurons. 6. Extracellular iontophoresis of a GABA uptake inhibitor, nipecotic acid, potentiated the effects of GABA. 7. Extracellular application of tetrodotoxin appeared to act pre- and postsynaptically to reduce respiratory fluctuations in membrane potential and to increase input resistance without altering the effects of iontophoresed glycine and GABA, suggesting that the amino acids act on postsynaptic membrane receptors not linked to fast sodium channels.(ABSTRACT TRUNCATED AT 400 WORDS)
