Abstract
The 2P domain K(+) channel TASK-3 is highly expressed in cerebellar granule neurons where it has been proposed to underlie the K(+) leak conductance, IKso. In a previous work we showed that expression of TASK-3 increases in cerebellar granule neurons as they mature in culture. Here we show that within the cerebellum, levels of TASK-3 mRNA increase as granule neurons migrate to their adult positions and receive excitatory mossy fiber input. To understand the mechanism of this increase in TASK-3 expression we used an in vitro model culturing the neurons in either depolarizing conditions mimicking neuronal activity (25K, 25 mm KCl) or in conditions which approach deafferentation (5K, 5 mm KCl). An important increase in TASK-3 mRNA is uniquely observed in 25K and is specific since other background K(+) channel levels remain unchanged or decrease. The rise in TASK-3 mRNA leads to an increase in TASK-3 protein and the IKso conductance resulting in hyperpolarization. Blocking L-type calcium channels or their downstream effector calcineurin, abrogates TASK-3 expression and IKso, leading to hyperexcitability. This is the first study demonstrating that depolarization-induced Ca(2+) entry can directly regulate cellular excitability by dynamically regulating the transcription of a resting K(+) conductance. The appearance of this conductance may play an important role in the transition of depolarized immature neurons to their mature hyperpolarized state during neuronal development.
Highlights
Since it behaves as a leak conductance and is inhibited by the activation of muscarinic acetylcholine receptors [4, 5]
Cerebellar granule neurons (CGNs) initially localized in the external granule layer (EGL) migrate across the molecular layer to reach the internal granule layer (IGL)
We have previously shown that the level of TASK-3 mRNA increases as a function of cerebellar development [17]
Summary
Since it behaves as a leak conductance and is inhibited by the activation of muscarinic acetylcholine receptors [4, 5]. These findings show that the rTASK-3 were labeled, while cells transfected with the increase of TASK-3 mRNA levels in granule neurons coincides rTASK-1 subunit or the vector alone were not fluorescent (supwith their arrival in the IGL and suggest that depolarization due plemental Fig. 1B).
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