Subthreshold inward membrane currents in guinea-pig frontal cortex neurons

Current-clamp and single-electrode voltage-clamp recordings were used to st udy the inward currents activated in the subthreshold membrane potential ra nge of cortical pyramidal neurons. The experiments were done on slices from guinea-pig frontal cortex and all recordings were obtained at a distance o f 600-900 mu m from the pial surface. In current-clamp recordings and from membrane potentials hyperpolarized to about -70 mV, the depolarization lead ing to spike firing was partially blocked by 1 mu M retrodotoxin, but not b y calcium-free extracellular solution, The calcium-free solution only affec ted this depolarization when the membrane potential was held at a level mor e negative than -75 mV. Under voltage-clamp, an inward current was recorded between the resting membrane potential and the level of spike firing. This current was activated at about - 60 mV and part of it was blocked by 1 mu M tetrodotoxin; the remaining current was blocked by calcium-free extracell ular solution. In five neurons both components were recorded and isolated i n the same cell, The tetrodotoxin-sensitive component activated at close to -60 mV, was similar to the persistent sodium current (INa-p) The Ca2+-sens itive component activated at close to -60 or -65 mV, was less voltage-depen dent than INa-p This component was similar to the low threshold calcium cur rent (I-T). These results suggest that the subthreshold depolarization which led to spi ke firing was dependent on INa-p and I-T, INa-p being the most important fa ctor up to resting membrane potentials of -70 or -75 mV. A physiological ro le of this finding is revealed by the action of dopamine, which (at 10 mu M ) prevented the firing of action potentials from -60 mV, but nor from -80 m V due to the inhibition of INa-p and the lack of effect on I-T. (C) 1999 IB RO. Published by Elsevier Science Ltd.