1 S ,3 R -ACPD induces a region of negative slope conductance in the steady-state current-voltage relationship of hippocampal pyramidal cells Luthi, Anita, Beat H. Gahwiler and Urs Gerber. Brain Research Institute, August Forel-Strasse 1, CH-8029 Zurich, Switzerland.
APStracts 3:0189N, 1996.
Synaptic responses mediated by metabotropic glutamate receptors (mGluRs) display a marked voltage-dependent increase in amplitude when neurons are moderately depolarized beyond membrane potential. We have investigated the basis for this apparent non-linear behavior by activating mGluRs with 1 S ,3 R -ACPD (10 [mu] M) in CA3 pyramidal cells from rat hippocampal slice cultures using the single-electrode voltage-clamp technique. Under control conditions, cells depolarized from resting potential by 10-20 ? mV responded with delayed outwardly rectifying currents due to activation of voltage- and Ca 2+ - dependent K + conductances. In contrast, in the continuous presence of 1 S ,3 R -ACPD, small depolarizations (10-20 mV) induced a delayed inward current. The steady-state I/V relationship for this response displayed a region of negative slope conductance at potentials between -55 and -40 mV. The reversal potential of the corresponding 1 S ,3 R -ACPD-sensitive tail currents (- 93.0+/-2.2 mV) was close to E K , consistent with a mGluR-mediated suppression of K + current. Thus, when external [K + _ was increased to 8 mM, there was a positive shift in reversal potential to -76.9+/-5.1 mV. The depolarization- induced inward current in the presence of 1 S ,3 R -ACPD was blocked by Ba 2+ (1 mM). The response was not dependent on changes in intracellular Ca 2+ concentration and was insensitive to bath-applied Cs + (1 ? mM), ruling out a contribution of Ca 2+ -dependent currents or the inward rectifier I Q . Furthermore, the effect of 1 S ,3 R -ACPD was not mimicked by inhibiting I AHP and I M with low Ca 2+ saline (0.5 mM Ca 2+ , 10 mM Mg 2+ ) containing 10 mM TEA. A comparison of the responses induced by 1 S ,3 R -ACPD and NMDA showed that both induce an inward current with small depolarizations from resting potential but with different kinetics and Mg 2+ sensitivity. These results indicate that the suppression of K + currents in response to activation of mGluRs is markedly voltage-dependent, increasing at depolarized potentials and decreasing at hyperpolarized potentials. The negative slope conductance at membrane voltages positive to resting potential may underlie the amplification of mGluR-mediated responses when the membrane potential approaches action potential threshold.

Received 15 May 1996; accepted in final form 29 August 1996.
APS Manuscript Number J393-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996