My lab is primarily focused on investigating the regulation of cardiac function by the autonomic nervous system in both health and disease. The cardiac autonomic nervous system is composed of two branches, the sympathetic and the parasympathetic systems. While working together, but in opposing manner, these branches manage the autonomic tone and control cardiac contractility by modulating the activity of ion channels in cardiac myocytes. This regulatory mechanism relies on the generation of highly coordinated and localized signaling events inside the cell.
In disease conditions, such as heart failure, the specificity of subcellular signaling responses following autonomic activation is compromised, which can lead to dysregulation of ion channel activity and cardiac arrhythmias. These abnormal heart rhythms are potentially life-threatening and are a major contributor to sudden cardiac death, one of the leading causes of mortality worldwide.
To gain insights into the intricate intracellular processes crucial for cell signaling and ion channel regulation in cardiac myocytes, we employ a diverse array of biophysical methods. Notably, we use electrophysiological approaches like whole cell patch clamp recordings, and advanced imaging techniques such as superresolution microscopy, fluorescence resonance energy transfer (FRET), and confocal microscopy.
Our main objective is to uncover the factors responsible for disrupted subcellular signaling involved in the regulation of cardiac contractility. With this knowledge, we aim to identify innovative therapeutic solutions that could be used in the treatment of disease conditions.
- Agarwal SR, Sherpa RT, Moshal KS, Harvey RD. (2022) Compartmentalized cAMP signaling in cardiac ventricular myocytes. Cell Signal 89:110172. doi: 10.1016/j.cellsig.2021.110172.
- Sherpa RT, Fiore C, Moshal KS, Wadsworth A, Rudokas MW, Agarwal SR, Harvey RD. (2021) Mitochondrial A-kinase anchoring proteins in cardiac ventricular myocytes. Physiol Rep 9: e15015. doi: 10.14814/phy2.15015.
- Agarwal SR, Fiore C, Miyashiro K, Ostrom RS, Harvey RD. (2019) Effect of adenylyl cyclase type 6 on localized production of cAMP by beta-2 adrenergic receptors in human airway smooth muscle cells. J Pharmacol Exp Ther. 370:104-110.
- Agarwal SR, Gratwohl J, Cozad M, Yang PC, Colleen CE, Harvey RD. (2018) Compartmentalized cAMP signaling associated with lipid raft and non-raft domains in adult ventricular myocytes. Frontiers of Pharmacology. 9(332); doi: 10.3389/fphar.2018.00332.
- Agarwal SR, Miyashiro K, Latt H, Ostrom RS, Harvey RD. (2017) Compartmentalized cAMP responses to prostaglandin EP2 receptor activation in human airway smooth muscle cells. British Journal of Pharmacology. 174(16): 2784-2796.
- Agarwal SR, Clancy CE, Harvey RD. (2016) Mechanisms restricting diffusion of intracellular cAMP. Scientific Reports. 6: 19577; doi: 10.1038/srep19577
- Pugh SD, MacDougall DA, Agarwal SR, Harvey RD, Porter KE, Calaghan S. (2014) Caveolin contributes to the modulation of basal and beta-adrenoceptor stimulated function of the adult rat ventricular myocyte by simvastatin: a novel pleiotropic effect. PLoS One, September; 9(9):e106905.
- Agarwal SR, MacDougall DA, Tyser R, Pugh SD, Calaghan SC, Harvey RD. (2011) Effects of cholesterol depletion on compartmentalized cAMP responses in adult cardiac myocytes. J Mol Cell Cardiol , March;50(3):500-9.
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