Premium
Tuning the excitability of midbrain dopamine neurons by modulating the Ca 2+ sensitivity of SK channels
Author(s) -
Ji Huifang,
Hougaard Charlotte,
Herrik Kjartan Frisch,
Strøbæk Dorte,
Christophersen Palle,
Shepard Paul D.
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06735.x
Subject(s) - apamin , afterhyperpolarization , sk channel , bursting , chemistry , neuroscience , depolarization , biophysics , dopamine , gating , hyperpolarization (physics) , patch clamp , substantia nigra , electrophysiology , potassium channel , ion channel , biology , receptor , dopaminergic , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
Small conductance Ca 2+ ‐activated K + (SK) channels play a prominent role in modulating the spontaneous activity of dopamine (DA) neurons as well as their response to synaptically‐released glutamate. SK channel gating is dependent on Ca 2+ binding to constitutively bound calmodulin, which itself is subject to endogenous and exogenous modulation. In the present study, patch‐clamp recording techniques were used to examine the relationship between the apparent Ca 2+ affinity of cloned SK3 channels expressed in cultured human embryonic kidney 293 cells and the excitability of DA neurons in slices from rat substantia nigra using the positive and negative SK channel modulators, 6,7‐dichloro‐1 H ‐indole‐2,3‐dione‐3‐oxime and R‐ N ‐(benzimidazol‐2‐yl)‐1,2,3,4‐tetrohydro‐1‐naphtylamine. Increasing the apparent Ca 2+ affinity of SK channels decreased the responsiveness of DA neurons to depolarizing current pulses, enhanced spike frequency adaptation and slowed spontaneous firing, effects attributable to an increase in the amplitude and duration of an apamin‐sensitive afterhyperpolarization. In contrast, decreasing the apparent Ca 2+ affinity of SK channels enhanced DA neuronal excitability and changed the firing pattern from a pacemaker to an irregular or bursting discharge. Both the reduction in apparent Ca 2+ affinity and the bursting associated with negative SK channel modulation were gradually surmounted by co‐application of the positive SK channel modulator. These results underscore the importance of SK channels in ‘tuning’ the excitability of DA neurons and demonstrate that gating modulation, in a manner analogous to physiological regulation of SK channels in vivo , represents a means of altering the response of DA neurons to membrane depolarization.