INTRACELLULAR ACIDIFICATION REDUCED GAP JUNCTION COUPLING BETWEEN IMMATURE RAT NEOCORTICAL PYRAMIDAL NEURONES

1. Developmental changes in electrophysiological properties of pyramid al neurones correlated with the developmental decline in gap junction- dependent dye coupling were investigated in coronal slices of rat pref rontal and sensorimotor cortex. Effects of intracellular acidification induced by application of weak organic acids on neuronal dye coupling , electrotonic parameters as well as synaptic potentials were examined using the patch clamp technique. Optical monitoring of intracellular pH revealed an acidic shift of 0.4-0.5 pH units following sodium propi onate application. 2. Dye coupling between layer II-III neurones was p rominent during the first two postnatal weeks. During this period, pre -incubation of slices with 30 mar of the sodium salts of weak organic acids reduced the number of cells coupled to the injected neurone by 6 4%. 3. Between postnatal days 1 and 18, the mean neuronal input resist ance decreased significantly (by 81.0%). Both the membrane time consta nt (tau(0)) and the first equalizing time constant (tau(1)) also showe d a significant developmental decline of 25.8 and 65.8%, respectively. Electrotonic length decreased by 34.9%. The electrophysiological prop erties of neurones displayed a pronounced intercellular variability wh ich decreased with on-going development. 4. During the first two postn atal weeks, intracellular acidification led to a mean increase in neur onal input resistance of 55.9% and a mean decrease in electrotonic len gth of 22.2%. The membrane time constant was reduced by approximately 25% in the majority of neurones tested. Significant electrophysiologic al effects induced by intracellular acidification were not detected in uncoupled neurones from 18-day-old rats. 5. EPSP width at half-maxima l amplitude showed a substantial reduction of approximately 50%, while rise times of the non-NMDA receptor-mediated EPSP components displaye d no significant change during development. Both weak organic acids, a s well as the gap junction blocker 1-octanol, reduced excitatory synap tic transmission independent of developmental age. 6. We conclude that gap junction permeability is regulated by intracellular pH in develop ing layer II-III pyramidal cells in the rat neocortex. The prominent c orrelation between pH-induced reduction in dye coupling and changes in electrophysiological cell properties suggests a significant influence of gap junctions on synaptic integration and information transfer in the immature neocortex.