Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed Mg2؉ -permeable ion channel fused to a C-terminal ␣-kinase domain. Recently, aldosterone was shown to increase intracellular Mg 2؉ levels and alter inflammatory signaling in TRPM7-expressing HEK293 cells. This study was undertaken to assess whether these effects were related to an aldosterone-mediated increase of TRPM7 current and/or plasma membrane localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h application of aldosterone significantly increased TRPM7 current and TRPM7 plasma membrane protein expression by 48% and 34%, respectively. The aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the serum-and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases the plasma membrane expression of TRPM7, which is associated with an increase of TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade involving SGK1 and a functioning TRPM7 ␣-kinase domain. We suggest that this mechanism may be of general relevance when interpreting the effects of aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and SGK1 are ubiquitously expressed.

The authors report a series of 100 brachial plexus injuries between April 1974 and January 1979. The frequency of these lesions, knowledge of the anatomy and pathology, and trends in prognosis are correlated to give the surgical indications for nerve graft repair. Correlation between preoperative myelography and the anatomy and type of pathology demonstrated at the time of operation, have been of special interest and have consolidated tha operative indications. Out of the 100 cases operated on between April 1974 and January 1979, neurolysis without plexus repair was performed in 25, nerve grafts for one, two or five roots in 64, and in nine cases, intercostal nerve or spinal accessory nerve transplantation was carried out. Forty-eight cases with a follow up of more than two years have been specially studied to give some indication of the therapeutic choice depending on the number of usable nerve roots. If only one usable root is present, it is clearly impossible to graft the whole plexus and the supra-scapular nerve and lateral cord (musculo-cutaneous nerve, lateral pectoral nerve and lateral head of median nerve) are given priority. If two roots can be grafted, we also bridge the radial nerve in the posterior cord. Our statistics confirm that the direct repair of these nerve lesions gives hopeful results and the functional improvements justify this type of surgery. The best results come from repair of the C5 and C6 nerve roots with re-innervation of the shoulder and elbow. In a complete palsy, when there are only one or two usable roots, loss of innervation of the hand will persist but the return of some function to the shoulder and elbow will allow a limited use of functional recovery. Our results prompt us to persist with methods founded on the precise and early indications for surgical treatment.

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