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      The Plasma Membrane Calcium ATPases and Their Role as Major New Players in Human Disease

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          Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism

          Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations in the potassium channel KCNJ5 that result in cell depolarization and Ca2+ influx cause ~40% of these tumors 1 . We found five somatic mutations (four altering glycine 403, one altering isoleucine 770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 non-KCNJ5-mutant APAs. These mutations lie in S6 segments that line the channel pore. Both result in channel activation at less depolarized potentials, and glycine 403 mutations also impair channel inactivation. These effects are inferred to cause increased Ca2+ influx, the sufficient stimulus for aldosterone production and cell proliferation in adrenal glomerulosa 2 . Remarkably, we identified de novo mutations at the identical positions in two children with a previously undescribed syndrome featuring primary aldosteronism and neuromuscular abnormalities. These findings implicate gain of function Ca2+ channel mutations in aldosterone-producing adenomas and primary aldosteronism.
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            Urinary bladder contraction and relaxation: physiology and pathophysiology.

            The detrusor smooth muscle is the main muscle component of the urinary bladder wall. Its ability to contract over a large length interval and to relax determines the bladder function during filling and micturition. These processes are regulated by several external nervous and hormonal control systems, and the detrusor contains multiple receptors and signaling pathways. Functional changes of the detrusor can be found in several clinically important conditions, e.g., lower urinary tract symptoms (LUTS) and bladder outlet obstruction. The aim of this review is to summarize and synthesize basic information and recent advances in the understanding of the properties of the detrusor smooth muscle, its contractile system, cellular signaling, membrane properties, and cellular receptors. Alterations in these systems in pathological conditions of the bladder wall are described, and some areas for future research are suggested.
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              Mechanisms of Pancreatic  -Cell Death in Type 1 and Type 2 Diabetes: Many Differences, Few Similarities

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                Author and article information

                Journal
                Physiological Reviews
                Physiological Reviews
                American Physiological Society
                0031-9333
                1522-1210
                July 2017
                July 2017
                : 97
                : 3
                : 1089-1125
                Affiliations
                [1 ]Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom
                Article
                10.1152/physrev.00028.2016
                28566538
                fa91f7ef-e132-4b29-9eb5-b322d4a83a33
                © 2017
                History

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