3 results for Allen, DG

  • Roles of cardiac stretch-activated channels beyond mechano-electric coupling: stretch-enhanced force generation and muscular dystrophy

    Allen, DG; Ward, Marie-Louise (2011)

    Book item
    The University of Auckland Library

    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.

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  • Stretch-activated channels in the heart: contributions to length-dependence and to cardiomyopathy

    Ward, Marie-Louise; Williams, IA; Chu, Y; Cooper, Patricia; Ju, YK; Allen, DG (2008)

    Journal article
    The University of Auckland Library

    The stretch-induced increase in force production of ventricular muscle is biphasic. An abrupt increase in force coincides with the stretch, which is then followed by a slower response that develops over minutes (the slow force response or SFR). The SFR is accompanied by a slow increase in the magnitude of the intracellular Ca2+ transient, but the stretch-dependent mechanisms that give rise to this remain controversial. We characterized the SFR using right ventricular trabeculae from mouse hearts. Application of three different blockers of stretch-activated non-selective cation channels (SACNSC) reduced the magnitude of the SFR 60 s after stretch (400 mM streptomycin: from 86725% to 38714%, Po0.01, n ?? 9; 10 mM GdCl3: from 65721%, to 1277%, Po0.01, n ?? 7; 10 mM GsMTx-4 from 122740% to 1578%, Po0.05, n ?? 6). Streptomycin also decreased the increase in Ca2+ transient amplitude 60 s after the stretch from 43.5712.7% to 5.773.5% (Po0.05, n ?? 4), and reduced the stretch-dependent increase in intracellular Ca2+ in quiescent muscles when stretched. The transient receptor potential, canonical channels TRPC1 and TRPC6 are mechano-sensitive, non-selective cation channels. They are expressed in mouse ventricular muscle, and could therefore be responsible for stretch-dependent influx of Na+ and/or Ca2+ during the SFR. Expression of TRPC1 was investigated in the mdx heart, a mouse model of Duchenne???s muscular dystrophy. Resting Ca2+ was raised in isolated myocytes from old mdx animals, which was blocked by application of SAC blockers. Expression of TRPC1 was increased in the older mdx animals, which have developed a dilated cardiomyopathy, and might therefore contribute to the dilated cardiomyopathy.

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  • Stretch-activated channels in the heart: contribution to cardiac performance

    Ward, Marie-Louise; Allen, DG (2009)

    Book item
    The University of Auckland Library

    Stretch-activated ion channels are widely expressed in most cell types and play an important role in a variety of normal cell functions, including volume regulation and length detection. In the heart, transduction of mechanical energy into cellular responses is an essential component of cardiac function. The heart is passively stretched, and actively shortens in every cardiac cycle; in addition, longer-term changes in volume occur during exercise, and in diseases such as heart failure. In this article, we discuss the importance of stretch-activated ion channels as mechano-transducers in the heart, with emphasis on their contribution to the regulation of contractile performance. As well, the role of stretch-activated channels in modifying the electrical activity of the heart is also discussed.

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