Breeding and investigation of the role of inhibitory G protein in adenylyl cyclase type 5 and type 6 knockout mice.

The objective of these studies is to investigate the role of inhibitory G protein in cAMP compartmentation in mice lacking either type 5 and/or type 6 adenylyl cyclase (AC). We have been conducting studies upon the changes in heart contractile function of these mice (under the approved protocols of 4892 & breeding mice 4958). We will now study the molecular mechanisms underlying compartmentation of beta-adrenergic receptor signaling in these mice. The mice are phenotypically normal. The studies are conducted on ex-vivo hearts harvested from anesthetized mice, so the animals experience no pain. These studies will help to understand how heart contractility is regulated by inhibitory G protein which has a beneficial role in heart failure, thus results of these studies may lead to new treatment for heart failure. Wild type C57/BL6 mice (125) or mice with knockout of AC5 (125), AC6 (125) or AC5,6 (205) will be used for the studies.

In addition, we will study the effect of pertussis toxin to modify phosphodiesterase activity in rat heart cells.