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, ? and ?. 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? or I? isoform of cGKI in smooth muscle (sm-cGKI? or sm-cGKI? 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? and sm-cGKI? mice. EFS induced a fast transient relaxation in muscles from sm-cGKI? and sm-cGKI? 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? mice than in muscles from sm-cGKI? mice. The different kinetic of recovery from relaxation after EFS in sm-cGKI? and sm-cGKI? mice suggests that different signaling pathways exist for each cGKI isoform in vivo in fundus muscles.     «

cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, ? and ?. 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? or I? isoform of cGKI in smooth muscle (sm-cGKI? or sm-cGKI? mice) were compared to muscles from con...     »