H+ ion signalling in heart and cancer

Intracellular pH (pHi), a measure of the cytoplasmic H+ ion concentration, is a fundamental controller of cell function. H+ ions are universal end-products of metabolism. Because of their high chemical reactivity, they must be extruded from cells. Displacements of pHi from its normal value of 7.20 modulate many signalling, developmental and physiological pathways within cells, including Ca2+ signalling, electrical excitation, muscle contraction, cell proliferation, and tumour development & invasiveness. In his seminar, Professor Vaughan-Jones will compare cellular strategies for regulating pHi in a highly differentiated organ, the heart, with those adopted by 3-D growths of tumour cells. Strategies include the spatially organised membrane expression of H+ and HCO3- ion transport proteins (eg. NHE & NBC isoforms), intercellular H+-ion co-ordination via multimeric connexin channels (eg. Cx 43 & 45), and the developmental importance of carbonic anhydrase enzyme isoforms, such as CAII and CAIX. Elucidation of the mechanisms controlling intracellular and extracellular H+-ion signalling, is helping to identify novel, potential targets in the treatment of heart disease and cancer.