No abstract

The TRPC6 channel is permeable to calcium ions as well as other ions and plays an important role in the physiology and pathophysiology of vessels. Findings from animal and cell culture experiments have shown its involvement in important vascular processes such as the Bayliss effect or endothelial-mediated vasodilatation. Furthermore, the relevance of TRPC6 channels in humans has become apparent based on diseases such as idiopathic pulmonary arterial hypertension, focal segmental glomerulosclerosis and atherosclerosis, amongst others. However, histological evidence that systematically detects TRPC6 channels in human vessels has not been provided to date. In this study, 40 vessel sections from nine body donors were obtained, processed and stained with a knockout-validated antibody against the TRPC6 protein using immunohistochemistry and western blotting. More than half of the samples yielded evidence of TRPC6 channel expression in the intima and adventitia. TRPC6 channels were detected in the tunica media in only one of 40 cases. TRPC6 detection in the human intima confirmed several demonstrated physiological aspects of the TRPC6 channels in the vasculature and may also be involved in associated human diseases. The near absence of TRPC6 channels in the tunica media was in contrast to a view that is primarily based on animal studies, from which its presence was assumed.

Transient receptor potential channel 6 (TRPC6) channels constitute non-selective cation channels that are localized in the plasmalemma or sarcolemma, and have a leading permeability for the bivalent calcium ion. Animal models indicate an involvement of TRPC6 in malignant hyperthermia. The expression of TRPC6 in the sarcolemma has been demonstrated in the skeletal muscle fibers of mice. The importance of TRPC6 channels for the influx of calcium into the muscle cell has also been established. The presence of TRPC6 in tissues of human skeletal muscle is surmised. In order to confirm the presence of TRPC6 in human skeletal muscle, tissue samples of various skeletal muscles (Musculus deltoideus, pectoralis major, trizeps brachii and rectus femoris) from eight different human donors (n=8; six preserved cadavers and two non-preserved cadavers) were examined using immunohistochemistry. TRPC6 was found in all muscle fibers of all investigated bodies. Appropriate controls yielded the expected results. As demonstrated in animal studies and in studies of human cells, the presented results confirmed the presence of TRPC6 in human skeletal muscle tissue. Thus, TRPC6 is most likely important for calcium homeostasis and the proper function of human muscle fibers and may be a target for treatment in various muscular diseases.