Regulation of rhythmic movements by purinergic neurotransmitters in frog embryos

Abstract

Many rhythmic motor behaviours, including swimming, walking, scratching, swallowing, micturition and sexual climax, are episodic: even in the absence of sensory inputs they exhibit a gradual run-down in frequency before spontaneously terminating. We have investigated whether the purinergic transmitters, ATP and adenosine, control run- down of swimming in the Xenopus embryo. By using specific agonists and antagonists for the purinergic receptors, we have shown that ATP (or a related substance) is released during swimming and activates P2y receptors to reduce voltage-gated K+ currents and cause an increase in the excitability of the spinal motor circuits. Adenosine is also produced during motor activity, possibly through the actions of ectonucleotidases. The activation by adenosine of P1 receptors reduces the voltage-gated Ca(2+) currents, lowers excitability of the motor circuits, and so opposes the actions of ATP. A gradually changing balance between ATP and adenosine therefore seems to underlie the run-down of the motor pattern for swimming in Xenopus. We believe this to be the first time that ATP and adenosine have been found to be involved in motor pattern generation. The antagonistic interplay between these two transmitters may offer a general feedback mechanism that underlies run-down of all episodic motor patterns in vertebrates.