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PROTON TRANSPORT GROUP |
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Research |
RESEARCH INTERESTS
Regulation of Intracellular pH in heart
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Influence of pHi on Ca2+i Many effects of pH on contraction in the heart are mediated through actions on the myofilaments and the Ca-binding protein, troponin C. Many other effects, however, are mediated through modulatory actions on intracellular Ca2+ signalling. We are investigating these actions. They are complex and often appear paradoxical. For example, acidosis can initially depress the Ca2+i transient that triggers contraction, but later on it can profoundly enhance the transient. Much of this latter effect forms the basis of the so-called “pH-paradox” that occurs during post ischaemic reperfusion of the heart. The scenario is that intracellular acid overload leads to intracellular Ca2+ overload and the appearance of triggered arrhythmias. A major part of the effect is mediated through overdrive of the acid extrusion proteins NHE and NBC, as inhibiting the transporters pharmacologically prevents much of the Ca2+overload and suppresses the arrhythmia. Selective inhibition of these transporters appears to be cardioprotective during post ischaemic reperfusion. Several selective inhibitors have been developed by the pharmaceutical industry as potential therapeutic agents for treatment of ischaemic disorders of the heart. |
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Influence of pHi on Ca2+i |