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Role of the intrinsic cardiac nervous system in myocardial ischaemia and arrhythmias

Grant


Scheme


  • Cardiovascular Senior Researcher Grants

Abstract


  • The heart is surrounded by a network of nerves (intrinsic cardiac nerves or ganglionated plexus) that densely innervate the heart, modulating heart rhythm and force of contraction. This network is interposed between brain and heart influencing the reciprocal signalling between both organs.There is compelling evidence that nerves innervating the heart trigger serious arrhythmias and affect survival in a range of cardiac diseases from coronary heart disease through to single gene disorders, with mounting evidence that intrinsic cardiac nerves mediate many of these effects. At present we have a very limited understanding of how these nerves communicate with each other and with the heart and we only have crude methods (e.g. burning or freezing the nerves) to deal with malfunction of intrinsic cardiac nerves. This project will look at the membrane receptors and ion channels that provide the molecular mechanisms by which nerves communicate, to help design better treatments.Ion channels are transmembrane proteins present in all living cells with > 400 distinct ion channels identified to date. Changes in ion channel expression and function can lead to the manifestation of various diseases, particularly in the cardiovascular system. The membrane receptors and ion channels in intrinsic cardiac ganglion neurons of the heart are a potential drug target. Modification of pathological cardiac function through ion channels expressed in the intrinsic cardiac nervous system is a plausible therapeutic strategy demanding development.The intra-cardiac neuronal network is linked to various cardiac diseases, including heart attack; angina; nerve damage caused by diabetes; and the infectious disease ¿Chaga¿s. In the context of heart attack, changes to intra-cardiac nerves during healing of the heart can often produce fatal arrhythmias. In my lab, I have developed techniques that allow an innovative approach to understanding the abnormal electrical behaviour of intra-cardiac nerves, including the ability to prepare and study whole mammalian intrinsic cardiac ganglion. These techniques can precisely guide the development of novel therapies or repurposing the currently available drugs for novel therapeutic interventions.The proposed research seeks to better understand intrinsic cardiac neurotransmission as a prerequisite to the development of new therapeutic approaches for treating common, serious life-threatening cardiovascular conditions. This research will help bu

Local Award Id


  • 133080

Scheme


  • Cardiovascular Senior Researcher Grants

Abstract


  • The heart is surrounded by a network of nerves (intrinsic cardiac nerves or ganglionated plexus) that densely innervate the heart, modulating heart rhythm and force of contraction. This network is interposed between brain and heart influencing the reciprocal signalling between both organs.There is compelling evidence that nerves innervating the heart trigger serious arrhythmias and affect survival in a range of cardiac diseases from coronary heart disease through to single gene disorders, with mounting evidence that intrinsic cardiac nerves mediate many of these effects. At present we have a very limited understanding of how these nerves communicate with each other and with the heart and we only have crude methods (e.g. burning or freezing the nerves) to deal with malfunction of intrinsic cardiac nerves. This project will look at the membrane receptors and ion channels that provide the molecular mechanisms by which nerves communicate, to help design better treatments.Ion channels are transmembrane proteins present in all living cells with > 400 distinct ion channels identified to date. Changes in ion channel expression and function can lead to the manifestation of various diseases, particularly in the cardiovascular system. The membrane receptors and ion channels in intrinsic cardiac ganglion neurons of the heart are a potential drug target. Modification of pathological cardiac function through ion channels expressed in the intrinsic cardiac nervous system is a plausible therapeutic strategy demanding development.The intra-cardiac neuronal network is linked to various cardiac diseases, including heart attack; angina; nerve damage caused by diabetes; and the infectious disease ¿Chaga¿s. In the context of heart attack, changes to intra-cardiac nerves during healing of the heart can often produce fatal arrhythmias. In my lab, I have developed techniques that allow an innovative approach to understanding the abnormal electrical behaviour of intra-cardiac nerves, including the ability to prepare and study whole mammalian intrinsic cardiac ganglion. These techniques can precisely guide the development of novel therapies or repurposing the currently available drugs for novel therapeutic interventions.The proposed research seeks to better understand intrinsic cardiac neurotransmission as a prerequisite to the development of new therapeutic approaches for treating common, serious life-threatening cardiovascular conditions. This research will help bu

Local Award Id


  • 133080