Inhibition of GABA uptake potentiates the conductance increase produced by GABA-mimetic compounds on single neurones in isolated olfactory cortex slices of the guinea-pig
Physiology Department, Queen's University of Belfast, The Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL
- 1Membrane potential and input conductance were recorded in single neurones in slices of guinea-pig olfactory cortex in vitro. γ-Aminobutyric acid (GABA) and GABA-mimetic compounds were applied by bath-perfusion. Potency was measured as the concentration required to double the input conductance.
- 2The potency of GABA was increased (i.e. the equi-effective concentrations were reduced) by 15.5 ± 2.3 times (mean ± s.e.mean) on reducing external [Na+] from 144 to 20 mmol l−1, by replacement with Mg2+. Corresponding potency changes for other agonists were + 10.8 ± 2.5 for 3-aminopropanesulphonic acid (3-APS); 3.25 ± 1.06 for isoguvacine and 2.43 ± 0.69 for muscimol.
- 3Nipecotic acid (0.5 mm) produced the following increases in potency: GABA 2.68 ± 0.82; 3-aminopropanesulphonic acid, 3.11 ± 0.07; isoguvacine, 1.92 ± 0.34; muscimol, 2.24 ± 0.17.
- 4The concentration of GABA in the bathing fluid necessary to double input conductance increased with increasing depth of the recording site from the cut surface. The apparent potency fell 10 times for each 60 μm depth increment up to 150 μm. The recording depth also affected the apparent potency of muscimol and 3-APS but to a lesser extent. Reduction of external [Na+] reduced the depth-dependence of both GABA and 3-APS potency.
- 5No clear change in the duration of the recurrent inhibitory postsynaptic conductance could be detected in the presence of 0.5 mmol l−1 nipecotic acid.
- 6It is suggested that agonist uptake by a Na+-dependent, nipecotic acid-sensitive mechanism severely attenuates the responses of olfactory neurones to exogenous GABA and to its analogues 3-APS, muscimol and isoguvacine, but has little immediate influence on the duration of the GABA-mediated inhibitory postsynaptic conductance.