A Ca2+-independent slow afterhyperpolarization in substantia nigra compacta neurons

The discharge properties of dopaminergic neurons in substantia nigra are influenced by slow adaptive responses, which have not been fully identified. The present study describes, in a slice preparation from the rat, a complex after hyperpolarization (AHP), elicited by action potential trains. The AHP could be subdivided into a fast component (AHP(f)), which was generated near action potential threshold, relaxed within approximately 1 s, and had highest amplitude when evoked by short-lasting (0.1 s) depolarizations, and a slow component (AHP(s)), which lasted several seconds, was evoked from subthreshold potentials, and required prolonged depolarizing stimuli (>0.1 s). A large proportion of the AHPf was sensitive to (i) 0.1 muM apamin, (ii) the Ca2+ antagonists, Cd2+ (0.2 mM) and Ni2+ (0.3 mM), (iii) low (0.2 mM) extracellular Ca2+ concentration, and (iv), Ca2+ chelation with intracellular EGTA. The AHP(s) was resistant to the above treatments, and it was insensitive to 25 muM dantrolene or prolonged exposure to 1 muM thapsigargin. The reversal potential of the AHP(s) (-97 mV) was close to the K+ equilibrium potential. It was significantly inhibited by 5 mM 4-aminopyridine, 5 muM haloperidol, 10 muM terfenadine, or high extracellular Mg2+ (10 mM), but not by 30 mM tetraethylammonium chloride, 50 muM carbachol, 0.5 muM glipizide, 2 muM (-)sulpiride, 100 muM N-allyl-normetazocine, or 100 muM pentazocine. Haloperidol reduced the post-stimulus inhibitory period seen during spontaneous discharge, but had no detectable effect on spike frequency adaptation. It is concluded that the SK-type Ca2+-activated K+ channels underlies a major component of the AHP(f), whereas the AHP(s) is call-independent and relies, in part, on a voltage-dependent K+ current with properties resembling the ether-a-go-go-related gene K+ channel. The latter component exerts a slow, spike-independent, inhibitory influence on repetitive discharge and contributes to the prolonged decrease in excitability following sustained depolarizing stimuli. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.