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Neuroscience. 2004;125(4):841-52.

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

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Department of Physiology, University of Aarhus, Ole Worms Alle 160, DK-8000 AArhus C, Denmark.


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.

[Indexed for MEDLINE]

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