Abstract:
Developed force in cardiac muscle increases in two phases following stretch; a rapid component due to increased overlap of thick and thin filaments coupled to an increase in calcium sensitivity; a slow phase caused by increased calcium-activated force. We have proposed that increased calcium entry through a calcium-permeable stretch-activated channel is responsible for the slow phase. In this chapter we discuss candidate genes that may encode this stretch-activated channel focusing on TRPC1, TRPC6 and TRPV2. While stretch-activated channels were first recognised by their increased activity when stretched in a patch-pipette, this does not appear to be the dominant physiological pathway of activation. Instead complex pathways including integrins, angiotensin, NADPH oxidase and ROS appear to be involved. Stretch-activated channels may also have roles in disease. For instance stretch-activated channels are over-active in skeletal muscle in Duchenne muscular dystrophy and appear to have role in the calcium entry which is a central pathological pathway of this disease. Cardiac muscle is also affected in Duchenne muscular dystrophy and stretch-activated channels may have a role in the dilated cardiomyopathy which develops.
