POSTNATAL MATURATION OF RAT HYPOTHALAMONEUROHYPOPHYSEAL NEURONS - EVIDENCE FOR A DEVELOPMENTAL DECREASE IN CALCIUM-ENTRY DURING ACTION-POTENTIALS

Action potentials and voltage-gated currents were studied in acutely d issociated neurosecretory cells from the rat supraoptic nucleus during the first the postnatal weeks (PW1-PW3), a period corresponding to th e final establishment of neuroendocrine relationships. Action potentia l duration (at half maximum) decreased from 2.7 to 1.8 ms; this was at tributable to a decrease in decay time. Application of cadmium (250 mu M) reduced the decay time by 43% at PW1 and 21% at PW3, indicating th at the contribution of calcium currents to action potentials decreased during postnatal development The density of high-voltage-activated ca lcium currents increased from 4.4 to 10.1 pA/pF at postnatal days 1-5 and 11-14, respectively. The conductance density of sustained potassiu m current, measured at +20 mV, increased from 0.35 (PW1) to 0.53 (PW3) nS/pF. The time to half-maximal amplitude did not change. Conductance density and time- and voltage-dependent inactivation of the transient potassium current were stable from birth. At PW1, the density and tim e constant of decay (measured at 0 mV) were 0.29 nS/pF (n = 12) and 17 .9 ms (n = 10), respectively. Voltage-dependent properties and density (1.1 nS/pF) of the sodium current did not change postnatally. During PW1, fitting the mean activation data with a Boltzmann function gave a half-activation potential of -25 mV. A double Boltzman equation was n ecessary to adequately fit the inactivation data, suggesting the prese nce of two populations of sodium channels. One population accounted fo r similar to 14% of the channels, with a half-inactivation potential o f -86 mV; the remaining population showed a half-inactivation potentia l of -51 mV. A mathematical model, based on Hodgkin-Huxley equations, was used to assess the respective contributions of individual currents to the action potential. When the densities of calcium and sustained potassium currents were changed from immature to mature values, the de cay time of the action potentials generated with the model decreased f rom 2.85 to 1.95 ms. A similar reduction was obtained when only the de nsity of the potassium current was increased. Integration of the calci um currents generated during mature and immature action potentials dem onstrated a significant decrease in calcium entry during development. We conclude that the developmental reduction of the action potential d uration 1) is a consequence of the developmentally regulated increase in a sustained potassium current and 2) leads to a reduction of the pa rticipation of calcium currents in the action potential, resulting in a decreased amount of calcium entering the cell during each action pot ential.