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 afterhyperpolarization (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 AHP(f) was sensitive to (i) 0.1 microM apamin, (ii) the Ca(2+) antagonists, Cd(2+) (0.2 mM) and Ni(2+) (0.3 mM), (iii) low (0.2 mM) extracellular Ca(2+) concentration, and (iv), Ca(2+) chelation with intracellular EGTA. The AHP(s) was resistant to the above treatments, and it was insensitive to 25 microM dantrolene or prolonged exposure to 1 microM 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 microM haloperidol, 10 microM terfenadine, or high extracellular Mg(2+) (10 mM), but not by 30 mM tetraethylammonium chloride, 50 microM carbachol, 0.5 microM glipizide, 2 microM (-)sulpiride, 100 microM N-allyl-normetazocine, or 100 microM 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 Ca(2+)-activated K(+) channels underlies a major component of the AHP(f), whereas the AHP(s) is Ca(2+)-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.
Nedergaard
S
S
Department of Physiology, University of Aarhus, Ole Worms Alle 160, DK-8000 AArhus C, Denmark. sn@fi.au.dk
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000502:physiology*
D002118:Calcium; D004298:Dopamine