Synchronous firing of inhibitory interneurons results in saturation of fast GABA(A) IPSC magnitude but not saturation of fast inhibitory efficacy in rat neocortical pyramidal cells.
The kinetic properties of evoked fast inhibitory postsynaptic currents were examined to elucidate factors underlying the limit on the magnitude of fast inhibition in neocortex. Using whole-cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex, fast gamma-aminobutyric acid-A (GABA[A])ergic inhibitory postsynaptic currents were selectively recorded by holding cells at potentials equal to excitatory postsynaptic current reversal (approximately 0 mV). As stimulus intensity was increased, the magnitude and duration of the fast inhibitory postsynaptic current increased. Over the range of stimuli applied (2-10 V), fast GABA(A)-mediated inhibitory postsynaptic currents reached a maximum peak conductance of 25.9 +/- 4.2 nS (range 10.5-41.2 nS) at intensities approximately 2-times threshold. As stimulus intensities were increased beyond this point of maximal conductance, the time constant of current decay increased as function of stimulus strength, while rise time remained unaffected. Exposure to nominally magnesium-free solutions did not affect maximal peak conductances of fast inhibitory postsynaptic currents, but did cause an increase in the time constants of current decay by 66.3 +/- 23.6%, resulting in an 85.6 +/- 24.6% increase in the total charge flux carried by single inhibitory postsynaptic currents. This effect may be due to prolonged activation of postsynaptic GABA(A) receptors by excess GABA released in response to increased excitation. Exposure to the GABA uptake blocker, nipecotic acid, similarly prolonged current decay without affecting the maximal peak conductance. Our findings suggest that the limit on recruitment of evoked fast inhibition in neocortical layer V pyramidal cells arises from the saturation of postsynaptic GABA(A) receptors. However, while there is a limit to the peak fast inhibitory postsynaptic conductance which can be recruited with increasing excitation, inhibitory strength may still be modulated by increasing charge flux through the prolongation of fast inhibition.
Ling
D S
DS
Department of Pharmacology, State University of New York, Health Science Center, Brooklyn 11203, USA. ling@hscbklyn.edu
Benardo
L S
LS
D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D019579:Neocortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009557:Nipecotic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D018756:GABA Antagonists; D009557:Nipecotic Acids; D010852:Picrotoxin; D011392:Proline; D011963:Receptors, GABA-A; C030278:nipecotic acid; C010983:homoproline