Crosstalk between the calcium sensing receptor and the renal NaCl cotransporter, NCC

Host: Dario Alessi

Venue: MSI Small Lecture Theatre, SLS

Abstract:

The activity of the NaCl cotransporter NCC in the distal convoluted tubule modulates arterial blood pressure since it defines the amount of salt excreted daily by the kidney.  The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that senses extracellular calcium concentration transforming this into secondary messengers. We have shown that a CaSR is present in the apical membrane of the DCT cells allowing the calcium concentration of the intratubular fluid to modulate the activity of NCC via the WNK4-SPAK kinase pathway. Our recent data suggest that the presence of glucose or fructose in the luminal fluid by a type II allosteric modulation on the CaSR (calcimimetic) increases the activity of NCC. This could have implications for the arterial hypertension that is associated with diabetes mellitus or the high consumption of fructose.

Bio:

Gerardo Gamba was born in Mexico City in 1961 and received MD and PhD degrees from the National University of Mexico. After Internal Medicine and Nephrology residencies in Mexico, he was appointed as a Fellow in Medicine at the Renal Division of the Brigham and Women’s Hospital (Harvard Medical School) from 1990 to 1993, under the training of Steven C. Hebert and Barry M. Brenner. He was the first to identify at the molecular level the cDNA encoding the thiazide-sensitive NaCl cotransporter (NCC) of the distal convoluted tubule, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb of Henle’s loop, and the Calcium Sensing Receptor (CaSR) from the parathyroid gland.

After his return from Boston in 1993 he joined the faculty of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) and the Instituto de Investigaciones Biomédicas of the National University of Mexico where he founded the Molecular Physiology Unit that is devoted to basic and clinical research in renal physiology, hypertension, and acute kidney injury.

As a physician scientist Dr Gamba devotes one or two months a year to the internal medicine and nephrology wards at the INCMNSZ. He has also been an active professor of physiology at the Faculty of Medicine of the National University of Mexico from 1993 to date, at the Universidad Panamericana from 2009 to date, La Salle University from 2003 – 2008, Tecnológico de Monterrey from 2011 to 2020 and in the nephrology residency at the INCMNSZ from 1993 to date.

Dr Gamba has received several accolades in his country, including the National Award in Science and Art in 2010 which is given in the field of Natural Science by the President of Mexico.