Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels

CALCITONIN gene-related peptide (CGRP) is a 37-amino-acid peptide produced by alternative processing of messenger RNA from the calcitonin gene1,2. CGRP is one of the most potent vasodilators known3. It occurs in and is released from perivascular nerves1,4 and has been detected in the blood stream5-7, suggesting that it is important in the control of blood flow8,9. The mechanism by which it dilates arteries is not known. Here, we report that arterial dilations in response to CGRP are partially reversed by blockers of the ATP-sensitive potassium channel (KATP), glibenclamide10-12 and barium10,13. We also show that CGRP hyperpolarizes arterial smooth muscle and that blockers of KATP channels reverse this hyperpolarization. Finally, we show that CGRP opens single K+ channels in patches on single smooth muscle cells from the same arteries. We propose that activation of KATP channels underlies a substantial part of the relaxation produced by CGRP.