Abstract
Rat mature cerebellar granule, unlike hippocampal neurons, die by apoptosis when cultured in a medium containing a physiological concentration of K+ but survive under high external K+ concentrations. Cell death in physiological K+ parallels the developmental expression of the TASK-1 and TASK-3 subunits that encode the pH-sensitive standing outward K+ current IKso. Genetic transfer of the TASK subunits in hippocampal neurons, lacking IKso, induces cell death, while their genetic inactivation protects cerebellar granule neurons. Neuronal death of cultured rat granule neurons is also prevented by conditions that specifically reduce K+ efflux through the TASK-3 channels such as extracellular acidosis and ruthenium red. TASK leak K+ channels thus play an important role in K+-dependent apoptosis of cerebellar granule neurons in culture.
Highlights
Rat mature cerebellar granule, unlike hippocampal neurons, die by apoptosis when cultured in a medium containing a physiological concentration of K؉ but survive under high external K؉ concentrations
TASK-1 is preferentially inhibited by anandamide, independently of the CB receptor [37], while TASK-3 is blocked by ruthenium red in the micromolar range [38]
Real-time PCR analysis revealed that the level of TASK-1 and TASK-3 transcripts gradually increased with time both in culture and in vivo (Fig. 2, A–B)
Summary
Unlike hippocampal neurons, die by apoptosis when cultured in a medium containing a physiological concentration of K؉ but survive under high external K؉ concentrations. Neuronal death of cultured rat granule neurons is prevented by conditions that reduce K؉ efflux through the TASK-3 channels such as extracellular acidosis and ruthenium red. TASK leak K؉ channels play an important role in K؉-dependent apoptosis of cerebellar granule neurons in culture. Cell excitability is a critical determinant of neuronal survival during brain development [1, 2] Kϩ channels set both the resting membrane potential and the action potential duration. We demonstrate that TASK-3 channels contribute to IKso and are involved in Kϩ-dependent rat granule neuronal death in culture
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