Frances Ashcroft
University of Oxford, UK
A physiologist discusses matters close to the heart.
This time last year my father was suffering from congestive heart failure. He became increasingly frail, slowing down like an unwound clockspring until, in February, his heart simply stopped.
As a physiologist, I had some idea of his condition, but I did not then realize how close it was to my own research area.
In 1983, ATP-sensitive potassium (K-ATP) channels were found in the heart. These channels are gated pores that control potassium fluxes across the cell membrane. However, their precise role in the heart was unclear.
One year later, I discovered that these channels are central to the mechanism by which glucose stimulates insulin secretion from the pancreas. Unravelling the role of K-ATP channels in diabetes, and the way in which channel structure influences function, has been an all-consuming passion for me ever since.
To my surprise, it now turns out that these channels also play a role in heart failure. Heart failure is usually caused by narrowing of the arteries, which increases the pressure against which the heart has to pump, making it work harder. Eventually, it fails.
Recently, Andre Terzic of the Mayo Clinic in Rochester, Minnesota, and his group showed that K-ATP channels confer protection against heart failure (S. Yamada et al. J. Physiol. Lond. published online doi:10.1113/jphysiol.2006.119511; 2006). In normal mice, cardiac K-ATP channels open in response to an increased pressure load, reducing stress on the heart. Mice lacking K-ATP channels rapidly develop heart failure and die.
In the pancreas, K-ATP-channel activity is finely balanced: too much causes diabetes and too little hyperinsulinism. But in the heart, as this paper shows, opening is almost always beneficial.
Comments
Frances Ashcroft’discussion on heart failure pathophysiology is really, clear, fascinating and up-dated. Since 1983, in Literature is referred the central role played by ATP-sensitive potassium (K-ATP) channels in heart activity.However, as CLINICIAN, I state that physicians all around the world have to know and bedside recognize in quantitative way the Inherited Real Risk of CAD and CVD, I have discovered and illustrated formerly (From Bibliography in my website, See for instance: 39. Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109, 1997; 156. Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php 2007; 116. Stagnaro Sergio. Biophysical-Semeiotic Bed-Side Detecting CAD, even silent, and Coronary Calcification. 4to Congreso International de Cardiologia por Internet, 2005, http://www.fac.org.ar/ccvc/marcoesp/marcos.php ; 151. Stagnaro Sergio. Old Age and Therapy for Coronary Artery Diseases. CMAJ. 28 September 2001. http://www.cmaj.ca/cgi/eletters/165/6/759 2001). Such as CAD and CVD Inherited Real Risk, based on newborn-pathological, subtype b) aspecific, type I, Endoarteriolar Blocking Devices, identical to those diabetic real risk is based on (140. Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1), may bring about ischaemic heart disorder, and subsequently heart failure, even decades later! As a consequence, nowadays we are able to perform a new more efficacious primary prevention of all common and serious diseases, including CAD, as I illustrated , e.g., on Ann Int Med.: 150. Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med.2007. http://www.annals.org/cgi/eletters/0000605-200708070-00167v1).
Posted by: Sergio Stagnaro MD | July 23, 2008 06:03 PM