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Elevation of intracellular Ca2+ modulates A-currents in rat cerebellar granule neurons

✍ Scribed by Xin Wang; Jie Bao; Xi-Min Zeng; Zheng Liu; Yan-Ai Mei

Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
399 KB
Volume
81
Category
Article
ISSN
0360-4012

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✦ Synopsis

In the brain, the transient-inactivating voltage-gated potassium channel currents (called I K(A) or A-currents) are activated at subthreshold membrane potentials to control the excitability of neurons. In the current study, the effect of intracellular calcium on the A-current and the action mechanism of intracellular calcium was investigated by using the whole-cell voltage-clamp technique. Elevation of intracellular calcium by addition of 2 mM CaCl 2 in the pipette solution significantly modulated both the peak amplitude and the kinetics of the A-current in rat granule neurons. The peak amplitudes of the A-current were 1,060 6 87 pA and 1,972 6 16 pA under conditions of no Ca 2þ and elevated intracellular Ca 2þ , respectively. The time to peak, the time course of fast inactivation, and the steady-state inactivation property of the A-current were all significantly altered by elevating the intracellular Ca 2þ . Replacement of the Ca 2þ in the pipette solution with the same concentration of Co 2þ did not mimic the effects of intracellular Ca 2þ on the A-current amplitude and kinetics. These effects are similar to the behavior of the reconstituted Kv4/KChIP (K V channel-interacting proteins) current induced by expression of KChIP and Kv4 together in a cell expression system. Application of 10 mM arachidonic acid, which can bind to the Kv4/KChIP complex, inhibited the A-current and eliminated the effects of intracellular Ca 2þ on the A-current, suggesting that KChIP may be involved in the effects of Ca 2þ on the A-current. Collectively, our results indicate that elevated intracellular Ca 2þ modulates the amplitude, fast activation, and steady-state inactivation characteristics of the A-current in rat cerebellar granule neurons, and this may occur via KChIP.

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