A TASK-like pH- and amine-sensitive 'leak' K+ conductance regulates neonatal rat facial motoneuron excitability in vitro.
A 'leak' potassium (K+) conductance (gK(Leak)) modulated by amine neurotransmitters is a major determinant of neonatal rat facial motoneuron excitability. Although the molecular identity of gK(Leak) 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(Leak). The pH-sensitive current (I(pH)), 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(NA)) was occluded at pH 6 and enhanced at pH 7.7. The TASK-1 selective inhibitor anandamide (10 microM), its stable analogue methanandamide (10 microM), the TASK-3 selective inhibitor ruthenium red (10 microM) and Zn2+ (100-300 microM) all failed to alter facial motoneuron membrane current or block I(NA) or I(pH). Isoflurane, a volatile anaesthetic that enhances heteromeric TASK-1/TASK-3 currents, increased gK(Leak). Ba2+, Cs+ and Rb+ blocked I(NA) and I(pH) voltage-dependently with maximal block at hyperpolarized potentials. 4-Aminopyridine (4-AP, 4 mM) voltage-independently blocked I(NA) and I(pH). In summary, gK(Leak) displays some of the properties of a TASK-like conductance. The linearity of gK(Leak) and an independence of activation on external [K+] suggests against pH-sensitive inwardly rectifying K+ channels. Our results argue against principal contributions to gK(Leak) by homomeric TASK-1 or TASK-3 channels, while the potentiation by isoflurane supports a predominant role for heterodimeric TASK-1/TASK-3 channels.
Larkman
Philip M
PM
Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK. P.Larkman@ed.ac.uk
Perkins
Emma M
EM
D000818:Animals; D000831:Animals, Newborn; D001679:Biogenic Amines / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology; D005152:Facial Muscles / Q000502:physiology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D009419:Nerve Tissue Proteins; D015221:Potassium Channels / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D001679:Biogenic Amines; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3