Role of the sodium/bicarbonate cotransporter (NBC) in the development of cardiac hypertrophy. Symposium: Acid-base transportres in the cardiovascular system

AIELLO EA

Simposio; Acta Physiologica International Symposium: H+ and HCO3- Physiology and Pathophysiology. 49th Sandbjerg Meeting on membrane Transport.; 2017

The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms in the cardiomyocytes, contributing to maintain intracellular pH (pHi) and sodium concentration ([Na+]i). Electroneutral (NBCn1; 1 Na+: 1 HCO3-) and electrogenic (NBCe1; 1 Na+: 2 HCO3-) isoforms of the NBC coexist in the heart. We have recently studied the expression and function of these isoforms in hearts of Wistar and spontaneously hypertensive rats (SHR), elucidating the direct implication of the renin-angiotensin-aldosterone system (RAAS) in the NBC regulation. We found an over-expression of NBCe1 and NBCn1 proteins in SHR that was prevented with the AT1 antagonist Losartan (Los-SHR). Despite the increase in NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in angiotensin II-induced hypertrophy. Whereas in SHR most of the pHi recovery from acidosis was due to NBCn1 stimulation, in Wistar and Los-SHR the activity of both isoforms was equitable, suggesting that the deteriorated cardiac NBCe1 function observed in SHR is compensated by an enhanced activity of NBCn1. Consistently, we observed greater level of internalized NBCe1 protein in endosomes near the nucleus in SHR than in the non-hypertophic groups, indicating defective trafficking to the membrane. We can then speculate that the upregulation of NBCn1, which carries more sodium to pull the same amount of bicarbonate than the NBCe1, could fairly contribute to [Na+]i and [Ca2+]i overload. Thus, the NBC isoforms remodelling described herein appears to be deleterious rather than compensatory and might be indeed involved in the development or progression of cardiac hypertrophy.