Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH- and halothane-sensitive K+ conductance.

The recently described two-pore-domain K+ channels, TASK-1 and TASK-3, generate currents with a unique set of properties; specifically, the channels produce instantaneous open-rectifier (i.e., "leak") K+ currents that are modulated by extracellular pH and by clinically useful anesthetics. In this study, we used histochemical and in vitro electrophysiological approaches to determine that TASK channels are expressed in serotonergic raphe neurons and to show that they confer a pH and anesthetic sensitivity to these neurons. By combining in situ hybridization for TASK-1 or TASK-3 with immunohistochemical localization of tryptophan hydroxylase, we found that a majority of serotonergic neurons in both dorsal and caudal raphe cell groups contain TASK channel transcripts (approximately 70-90%). Whole-cell voltage-clamp recordings were obtained from raphe cells that responded to 5-HT in a manner characteristic of serotonergic neurons (i.e., with activation of an inwardly rectifying K+ current). In those cells, we isolated an endogenous K+ conductance that had properties expected of TASK channel currents; raphe neurons expressed a joint pH- and halothane-sensitive open-rectifier K+ current. The pH sensitivity of this current (pK approximately 7.0) was intermediate between that of TASK-1 and TASK-3, consistent with functional expression of both channel types. Together, these data indicate that TASK-1 and TASK-3 are expressed and functional in serotonergic raphe neurons. The pH-dependent inhibition of TASK channels in raphe neurons may contribute to ventilatory and arousal reflexes associated with extracellular acidosis; on the other hand, activation of raphe neuronal TASK channels by volatile anesthetics could play a role in their immobilizing and sedative-hypnotic effects.

Cardiorespiratory neurons of the rat ventrolateral medulla contain TASK-1 and TASK-3 channel mRNA.

The potassium channels TASK-1 and TASK-3 are neuronal 'leak' channels that are inhibited by extracellular acidification and numerous neurotransmitters. Here we tested whether in the rat TASK-1 and TASK-3 mRNAs are present in ventrolateral medulla neurons that regulate respiration or circulation (C1 adrenergic neurons). The mRNAs were identified by in situ hybridization. Respiratory neurons were identified by anatomical markers (neurokinin-1 receptors, NK1R, or somatostatin) or directly by juxtacellular labeling of bulbospinal neurons. C1 neurons were identified by the presence of tyrosine-hydroxylase. TASK-1 and TASK-3 transcripts were present in all hypoglossal and facial motor neurons, in most C1 cells (85-95%), in most small and large NK1R-ir neurons (>90%) of the ventral respiratory group (VRG) and in all the inspiratory-augmenting bulbospinal neurons of the rostral ventral respiratory group. In conclusion, TASK channels are expressed by respiratory cells with putative rhythmogenic function and by premotor and motor neurons. TASK channels presumably mediate excitatory effects of numerous transmitters on these neurons and may contribute to their pH-sensitivity.

Expression of the tyrosine kinase receptor EphA5 and its ligand ephrin-A5 during mouse spinal cord development.

OBJECTIVES: To study the expression patterns of two Eph family molecules, the receptor EphA5, and the ligand ephrin-A5, during spinal cord development. METHODS: The receptor expression was analyzed using beta-galactosidase knockin mice, and affinity ligand probe binding. The ligand expression was assessed using two different affinity probes, and knockout mouse tissues as controls. RESULTS: EphA5 was expressed in the ventral spinal cord, while ephrin-A5 was located in the dorsolateral regions of the spinal cord throughout development. CONCLUSIONS: These results show that EphA5 and ephrin-A5 are expressed over broad developmental stages and may play important roles in establishing the dorsoventral organization of the spinal cord.