Chloride channels in vascular smooth muscle cells, either activated by volume like ClC-3 or by calcium like TMEM16A, are involved in hypertension genesis61–63, like the electroneutral sodium–potassium-chloride cotransporters, that sense intracellular chloride in vascular smooth muscle cells and neurons (NKCC1) and in the renal tubular fluid (NKCC2)64. The gene discussed is CLCN3; the disease is hypertensive disorder.