Alternative splicing of P2X6 receptors in developing mouse brain and during in vitro neuronal differentiation.

Adenosine triphosphate acts as a fast excitatory neurotransmitter by binding to and activating seven structurally related subtypes of purinergic P2X receptors, which act as ligand-gated ion channels. Besides its role in neurotransmission, ATP also has trophic functions during development of the neuronal system. P2X receptor expression, mainly of P2X(4) and P2X(6) subtypes, has been detected in adult brain and also during neuronal development. We have used the mouse teratocarcinoma P19 cell line as an in vitro model to study P2X(6) receptor expression during early neuronal differentiation. We have detected a full-length and an alternatively spliced form of the mouse P2X(6) receptor gene in P19 cells using reverse transcriptase-polymerase chain reaction. The alternatively spliced form was already present at the stage of pluripotent undifferentiated P19 cells, and was predominant compared to the full-length form during the whole course of neuronal differentiation of P19 cells. Alternative splicing of P2X(6) receptor subunits was also confirmed during postnatal development of mouse brain. During postnatal development, however, the full-length form was predominant compared to the spliced form. Alternative splicing is suggested to regulate P2X(6) receptor function during neuronal differentiation.