Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle

cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, alpha and beta. Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was analyzed in gastric fundus smooth muscle from mice. Muscles from mice that express selectively the I alpha or I beta isoform of cGKI in smooth muscle (sm-cGKI alpha or sm-cGKI beta mice) were compared to muscles from conventional cGKI(-/-) mice. Fundus muscles were contracted by carbachol and then relaxed by 8-Br-cGMP or by electrical field stimulation (EFS). The time course of relaxation by 8-Br-cGMP was not different between muscles from sm-cGKI alpha and sm-cGKI beta mice. EFS induced a fast transient relaxation in muscles from sm-cGKI alpha and sm-cGKI beta mice that was blocked by the NO synthase inhibitor L-NAME. Recovery from this relaxation was about 4-times slower in muscles from sm-cGKI alpha mice than in muscles from sm-cGKI beta mice. The different kinetic of recovery from relaxation after EFS in sm-cGKI alpha and sm-cGKI beta mice suggests that different signaling pathways exist for each cGKI isoform in vivo in fundus muscles. (C) 2011 Published by Elsevier B.V.