A TASK-like pH- and amine-sensitive ‘leak’ K+ conductance regulates neonatal rat facial motoneuron excitability in vitro

Autor: Emma M. Perkins, Philip M. Larkman
Rok vydání: 2005
Předmět:
Zdroj: European Journal of Neuroscience. 21:679-691
ISSN: 1460-9568
0953-816X
DOI: 10.1111/j.1460-9568.2005.03898.x
Popis: A 'leak' potassium (K + ) conductance (gK L e a k ) modulated by amine neurotransmitters is a major determinant of neonatal rat facial motoneuron excitability. Although the molecular identity of gK L e a k is unknown, TASK-1 and TASK-3 channel mRNA is found in facial motoneurons. External pH, across the physiological range (pH 6-8), and noradrenaline (NA) modulated a conductance that displayed a relatively linear current/voltage relationship and reversed at the K + equilibrium potential, consistent with inhibition of gK L e a k . The pH-sensitive current (I p H ), was maximal around pH 8, fully inhibited near pH 6 and was described by a modified Hill equation with a pK of 7.1. The NA-induced current (I N A ) was occluded at pH 6 and enhanced at pH 7.7. The TASK-1 selective inhibitor anandamide (10 μM), its stable analogue methanandamide (10 μM), the TASK-3 selective inhibitor ruthenium red (10 μM) and Zn 2 + (100-300 μM) all failed to alter facial motoneuron membrane current or block I N A or l p H . Isoflurane, a volatile anaesthetic that enhances heteromeric TASK-1/TASK-3 currents, increased gK L e a k . Ba 2 + , Cs + and Rb + blocked I N A and I p H voltage-dependently with maximal block at hyperpolarized potentials. 4-Aminopyridine (4-AP, 4 mM) voltage-independently blocked I N A and l p H . In summary, gK L e a k displays some of the properties of a TASK-like conductance. The linearity of gK L e a k and an independence of activation on external [K + ] suggests against pH-sensitive inwardly rectifying K + channels. Our results argue against principal contributions to gK L e a k by homomeric TASK-1 or TASK-3 channels, while the potentiation by isoflurane supports a predominant role for heterodimeric TASK-1/TASK-3 channels.
Databáze: OpenAIRE
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