Submitted on January 4, 2007
Accepted on April 28, 2007
Adenosine stimulates the basolateral 50 pS K channels in the thick ascending limb of the rat kidney
Ruimin Gu1, Jing Wang1, Yunhong Zhang1, Wennan Li1, Ying Xu1, Hongli Shan2, WenHui Wang3*, and Baofeng Yang2
1 Physiology, Harbin Medical University, Harbin, China
2 Pharmacology, Harbin Medical University, Harbin, China
3 Pharmacology, New York Medical College, Valhalla, New York, United States
* To whom correspondence should be addressed. E-mail: wenhui_wang{at}nymc.edu.
We used the patch-clamp technique to examine the effect of adenosine on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. A 50 pS inwardly-rectifying K channel was detected in the basolateral membrane and the channel activity was decreased by hyperpolarization. Application of adenosine (10 µM) increased the activity of basolateral 50 pS K channels, defined by NPo, from 0.21 to 0.41. The effect of adenosine on the 50 pS K channels was mimicked by cyclohexyladenosine (CHA) which increased channel activity by a dose-dependent manner. However, inhibition of the A1 adenosine receptor with 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) failed to block the effect of CHA. In contrast, application of 8-(3-chlorostyryl) caffeine (CSC), an A2 adenosine antagonist, abolished the stimulatory effect of CHA. The possibility that the effect of adenosine and adenosine analog on the basolateral 50 pS K channel was the result of activation of the A2 adenosine receptor was also suggested by the observation that application of CGS-21680, a selected A2A adenosine receptor agonist, increased the channel activity from 0.29 to 0.56. Also, inhibition of protein kinase A with H8 abolished the stimulatory effect of CHA on the basolateral 50 pS K. We conclude that adenosine activates the 50 pS K channel in the basolateral membrane of the TAL and the stimulatory effect is mainly mediated by a PKA-dependent pathway via the A2 adenosine receptor in the TAL.
