Dale N, Gilday D
School of Biological and Medical Sciences, University of St Andrews, UK.
Nature. 1996 Sep 19;383(6597):259-63. doi: 10.1038/383259a0.
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.
许多节律性运动行为，包括游泳、行走、抓挠、吞咽、排尿和性高潮，都是间歇性的：即使在没有感觉输入的情况下，它们在自发终止前频率也会逐渐降低。我们研究了嘌呤能递质ATP和腺苷是否控制非洲爪蟾胚胎游泳的频率降低。通过使用嘌呤能受体的特异性激动剂和拮抗剂，我们发现ATP（或一种相关物质）在游泳过程中释放，并激活P2y受体以减少电压门控钾电流，从而导致脊髓运动回路兴奋性增加。腺苷也在运动活动期间产生，可能是通过外核苷酸酶的作用。腺苷对P1受体的激活会减少电压门控钙电流，降低运动回路的兴奋性，因此与ATP的作用相反。因此，ATP和腺苷之间逐渐变化的平衡似乎是非洲爪蟾游泳运动模式频率降低的基础。我们认为这是首次发现ATP和腺苷参与运动模式的产生。这两种递质之间的拮抗相互作用可能提供了一种普遍的反馈机制，是脊椎动物所有间歇性运动模式频率降低的基础。
