Journal of Physiology (1993), 463, pp. 391-407 391 With 6 figures Printed in Great Britain CHARACTERIZATION OF SYNAPTICALLY ELICITED GABAB RESPONSES USING PATCH-CLAMP RECORDINGS IN RAT HIPPOCAMPAL SLICES BY THOMAS S. OTIS, YVES DE KONINCK AND ISTVAN MODY* From the Department of Neurology and Neurological Sciences, Stanford University Medical Center, Room MO 16, Stanford, CA 94305, USA (Received 9 April 1992) SUMMARY 1. Tight-seal, whole-cell voltage clamp recording techniques were used to characterize monosynaptically evoked GABAB currents in adult rat brain slices maintained at 34-35 'C. Responses were recorded from granule cells of the dentate gyrus following the blockade of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-, D-2- amino-5-phosphonovaleric acid (D-AP5)- and picrotoxin-sensitive fast synaptic transmission, so that the remaining synaptic currents could be studied in isolation. 2. Under these conditions, stimulation in the molecular layer elicited a slow outward current which was blocked by the selective GABAB antagonist CGP 35348 in a concentration-dependent manner (200-800 /LM). This current was absent in recordings made with pipettes containing 10-15 mm of the lidocaine derivative QX- 314 or when caesium was substituted for K+. 3. Increasing the [K+]o e-fold (from 2-5 to 6-8 mM) shifted the reversal potential of the GABAB current from -97-9 to - 73-2 mV, as predicted by the Nernst equation. Peak conductance was constant, but in 6-8 mm [K+]. at voltages hyperpolarized to EK (equilibrium potential for potassium), a small outward rectification was evident. 4. The time course of the current could be described by fourth-power exponential activation kinetics with double exponential inactivation. At 34-35 °C, the average activation time constant (Tm) was 45-2 ms, while the two inactivation time constants (,rh and Th2) were 110-2 and 516-2 ms, with corresponding weighting factors (wh, and Wh2) of 0-84 and 0-16, respectively. The Qlo (temperature coefficient) values for these time constants were between 1-82 and 2-31. Neither Tm, nor hl and Th2 were voltage dependent in the range from -45 to -95 mV. 5. Paired-pulse depression of the GABAB current was studied by giving identical conditioning and test stimuli over a wide range (50-5000 ms) of interstimulus intervals (ISIs). The maximal depression (48°%) occurred at 200 ms ISI, and the depression lasted for over 5 s. The magnitude of paired-pulse depression was not dependent on the postsynaptic membrane potential. 6. Application of the competitive antagonist CGP 35348 such that the peak current was diminished by approximately 50% had no effect on the activation or inactivation kinetics of the current. Similarly, during paired-pulse depression the * To whom correspondence should be sent. MS 1276 ) by guest on July 13, 2011 jp.physoc.org Downloaded from J Physiol (