Both intracellular pH (pHi) and synaptic cleft pH change during neuronal activity yet little is known about how these pH shifts might affect synaptic transmission by influencing vesicle fusion. To address this we imaged pH- and Ca2+-sensitive fluorescent indicators (HPTS, Oregon green) in boutons at neuromuscular junctions. Electrical stimulation of motor nerves evoked presynaptic Ca2+i rises and pHi falls (∼0.1 pH units) followed by recovery of both Ca2+i and pHi. The plasma-membrane calcium ATPase (PMCA) inhibitor, 5(6)-carboxyeosin diacetate, slowed both the calcium recovery and the acidification. To investigate a possible calcium-independent role for the pHi shifts in modulating vesicle fusion we recorded post-synaptic miniature end-plate potential (mEPP) and current (mEPC) frequency in Ca2+-free solution. Acidification by propionate superfusion, NH4+ withdrawal, or the inhibition of acid extrusion on the Na+/H+ exchanger (NHE) induced a rise in miniature frequency. Furthermore, the inhibition of acid extrusion enhanced the rise induced by propionate addition and NH4+ removal. In the presence of NH4+, 10 out of 23 cells showed, after a delay, one or more rises in miniature frequency. These findings suggest that Ca2+-dependent pHi shifts, caused by the PMCA and regulated by NHE, may stimulate vesicle release. Furthermore, in the presence of membrane permeant buffers, exocytosed acid or its equivalents may enhance release through positive feedback. This hitherto neglected pH signalling, and the potential feedback role of vesicular acid, could explain some important neuronal excitability changes associated with altered pH and its buffering. Synapse 67:729–740, 2013.

(1972). Brit. J. industr. Med., 29,[274][275][276][277][278][279]. Radiological survey of men exposed to asbestos in naval dockyards. Asbestos related abnormalities were found in 3 % of a 10 % sample population in radiological surveys of the naval dockyards at Portsmouth, Chatham, and Rosyth. The prevalence of these abnormalities was related to the type of occupation and duration of exposure to asbestos. The results confirm the findings of an earlier survey at Devonport dockyard.No association between smoking, or the amount smoked, and the incidence of parenchymal or pleural disease due to asbestos was detected.Pleural abnormalities were found 10 times more frequently than parenchymal disease, and concern is felt over the uncertainty of the prognosis in men with pleural abnormalities, especially as 37 men have developed pleural mesothelioma at Devonport since 1965.More work is required to establish the true significance of pleural abnormalities caused by asbestos and to explore possible methods of treatment.