Early postnatal development of substantia nigra neurons in rat midbrain slices: hyperpolarization-activated inward current and dopamine-activated current.

Abstract

Whole-cell voltage-clamp recordings in rat midbrain slices were used to determine the characteristics and postnatal development of a hyperpolarization-activated inward current (Ih) and a dopamine receptor-activated current of neurons in the substantia nigra pars compacta (SNC). Ih was activated by membrane hyperpolarization beyond the resting membrane potentials, and displayed strong inward rectification. No sign of time- and voltage-dependent inactivation was apparent. The reversal potential of Ih in mature (P12-P13) SNC neurons was -39.2 +/- 4.3 mV, and the activation curve of Ih was well fitted by a sigmoidal function with half-maximal activation at -114.0 +/- 5.6 mV. Those values are essentially the same in immature (P3-P5) neurons. The rate of Ih activation was best approximated by a single exponential function. The time constants were voltage dependent, ranging from 692.3 ms at -110 mV to 342.8 ms at -150 mV at P12 neurons, and 1142.5 ms at -110 mV to 593.2 ms at -150 mV at P3 neurons. There was a marked increase in the amplitude of Ih during postnatal development of SNC neurons, while the membrane capacitance did not alter after P5. The increase in Ih after P5 thus appears to result from an increase in Ih current density. Application of dopamine produced a hyperpolarization of mature SNC neurons, leading to suppression of action potentials. Dopamine-activated outward current was negligible during the first postnatal week, and increased rapidly after the second week. Our results indicate that the SNC neuron of the rat midbrain is not fully mature at the time of birth in terms of voltage-gated ion channels and neurotransmitter receptors, but develops over the first two postnatal weeks.