Mechanotransduction and Redox Signals

Why cover only one article in a podcast, when we can discuss five articles at once? In this podcast on a unique Review article, Associate Editor Nancy Kanagy (University of New Mexico) interviews senior author and symposium organizer Shampa Chatterjee (University of Pennsylvania) and leading expert Mark Nelson (University of Vermont) about five reports presented at the 1st Pan American Congress of Physiological Sciences: Physiology Without Borders held in August 2014 in Iguassu Falls, Brazil. Under the umbrella topic of mechanosignaling and downstream redox-dependent responses, what links the mechanical forces at the cell membrane to the intracellular responses? Several key new findings were presented at the meeting. Among them, researchers have found that numerous elements on the cytoskeleton, such as PECAM and caveolae (caveolin-1), work together to form a mechanosome. Is the key to understanding the response to mechanosensing defining the machinery within the multifarious mechanosomes? How do we translate observations in cultured cells to responses in intact tissues and animals? Listen and learn.

Shampa Chatterjee, Keigi Fujiwara, Nestor G. Perez, Masuko Ushio-Fukai, Aron B. Fisher Mechanosignaling in the Vasculature: Emerging Concepts in Sensing, Transduction and Physiological Responses Am J Physiol Heart Circ Physiol, published online April 11, 2015, DOI: 10.1152/ajpheart.00105.2015.


TTD Reverses Human Cardiac Myofibroblast Activation

How does Tetrandrine (TTD) directly affect human cardiac fibroblasts, and can it benefit heart failure patients? In this new podcast, Deputy Editor Merry Lindsey (University of Mississippi Medical Center) interviews lead author Paul Fedak (University of Calgary) and content expert Jason Gardner (Louisiana State University Health Sciences Center) about the exciting new work by Teng et al which investigates the potential therapeutic agent TTD, a calcium channel blocker with anti-fibrotic effects in human patients. In addition to in vivo studies, Fedak and co-authors used a unique micro gel technique to isolate a single human fibroblast and identify its influence on local matrix remodeling. Given that the primary dysfunction associated with heart failure with preserved ejection fraction (HFPEF) is reduced relaxation due to extensive fibrosis, the results shown by Fedak and colleagues are particularly interesting. TTD was shown in their animal model to reverse fibrosis and restore cardiac compliance in vivo, but had little effect on fibroblast production of collagen. What is next in this fascinating story? Listen to find out.

Guoqi Teng, Daniyil Svystonyuk, Holly E.M. Mewhort, Jeannine D. Turnbull, Darrell D. Belke, Henry J. Duff, Paul W.M. Fedak Tetrandrine reverses human cardiac myofibroblast activation and myocardial fibrosis Am J Physiol Heart Circ Physiol, published online April 11, 2015, doi: 10.1152/ajpheart.00126.2015.


MSNA and Trigeminal Nerve Stimulation

Ever wonder how the impressive diving reflex seen in seals might be related to human physiology? In this engaging podcast, Guest Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews lead author James P. Fisher (University of Birmingham, United Kingdom) and Zeljko Dujic (University of Split School of Medicine, Croatia) about a fascinating new study by Fisher and colleagues designed to investigate whether the sympathetic effects of the trigeminal nerve reflex have additive effects with the reflexes due to exercise. The authors used ice packs applied the face to stimulate the trigeminal nerve, and added handgrip exercise to evaluate whether excessive sympathoexcitation could result. What was the response of muscle sympathetic nerve activity when hand-grip exercise was added to the facial cooling-stimulation of the diving reflex? What implications does this study have for elite breath-hold divers, for recreational divers, or for patient populations who want to participate in water sports? Listen and find out.

James P. Fisher, Igor A. Fernandes, Thales C. Barbosa, Eliza Prodel, John H. Coote, Antonio Claudio L. Nóbrega, Lauro C. Vianna Diving and exercise: The interaction of trigeminal receptors and muscle metaboreceptors on muscle sympathetic nerve activity in humans Am J Physiol Heart Circ Physiol, published March 1, 2105, DOI: 10.1152/ajpheart.00728.2014.