HYPERPOLARIZATION-ACTIVATED INWARD CURRENTS CONTRIBUTE TO SPONTANEOUSELECTRICAL-ACTIVITY AND CO2 H+ SENSITIVITY OF CULTIVATED NEURONS OF FETAL-RAT MEDULLA/

Neurons growing out from cultivated fetal medullary slices that exhibi ted spontaneous electrical activity after blockade of synaptic transmi ssion were investigated by the patch-clamp technique for their respons e to decreases in the extracellular pH. Increases in the [H+] induced by increases in PCO2, resulted in a decrease in spike frequency associ ated with a decrease in the rate of depolarization preceeding each act ion potential. The type of ion channel, contributing to interspike dep olarization, and which may therefore be the site of CO2/H+ action, was identified by application of agents that inhibited the hyperpolarizat ion-activated cation, I-H, channel (Cs+ and ZD7288). Application of Cs + and ZD7288 slightly hyperpolarized the cell membrane, decreased the interspike slope and inhibited CO2/H+-induced modulations of spike fre quency in one group of CO2-inhibited medullary neurons, suggesting tha t I-H contributes to spontaneous neuronal activity and to CO2/H+-sensi tivity. CO2/H+ effects on I-H were further confirmed in voltage-clamp experiments. Increasing the bath CO2 from 2% to 9% reduced the I-H amp litude, shifted the mean E-H from -54 to -60 mV, lengthened the voltag e-dependent delay of current activation and increased the time-constan ts of activation at all potentials studied. It is concluded that depol arizing inward currents through I-H channels participate in the gradua l ramp-like change in membrane potential which depolarizes the cell up to the threshold of Na+ spike generation. CO2/H+-induced inhibition o f I-H reduces the contribution of this ion current to the interspike d epolarization and accounts for the CO2/H+-induced decrease in spike fr equency in one type of CO2/H+-inhibited medullary cells. (C) 1998 IBRO . Published by Elsevier Science Ltd.