On the effects of diabetes mellitus on the mechanical properties of DRG sensory neurons and their possible relation with diabetic neuropathy.

Diabetic neuropathy (DN) is one of the principal complications of diabetes mellitus (DM). Dorsal root ganglion (DRG) neurons are the primary sensory neurons that transduce mechanical, chemical, thermal, and pain stimuli. Diabetes-caused sensitivity alterations and presence of pain are due to cellular damage originated by persistent hyperglycemia, microvascular insufficiency, and oxidative and nitrosative stress. However, the underlying mechanisms have not been fully clarified. The present work addresses this problem by hypothesizing that sensitivity changes in DN result from mechanotransduction-system alterations in sensory neurons; especially, plasma membrane affectations. This hypothesis is tackled by means of elastic-deformation experiments performed on DGR neurons from a murine model for type-1 DM, as well a mathematical model of the cell mechanical structure. The obtained results suggest that the plasma-membrane fluidity of DRG sensory neurons is modified by the induction of DM, and that this alteration may correlate with changes in the cell calcium transient that results from mechanical stimuli.

Mechanosensitive ion channel inhibitors promote the stiffening of the plasma membrane of mouse sensory neurons.

The mechanosensitivity of cells depends on the lipid-protein interactions of the plasma membrane. Affectations in the lipid region of the plasma membrane affect the transduction of mechanical forces, and any molecule that modifies the biophysical integrity of the lipid bilayer can alter the mechanical activity of the proteins inside the membrane. To understand whether inhibitors of mechanically activated ion channels affect the mechanical properties of the plasma membrane, we evaluated the rigidity of the membrane of sensory neurons of the DRG of mice using a variant of the scanning ion conductance microscopy method, which allows us to calculate the Young's modulus of individual cells before and after the perfusion of different doses of Gd3+, ruthenium red and GsMTx-4. Our results suggest that these molecules compromise the membrane by increasing the Young's modulus value, which indicates that the membrane becomes more rigid; these compounds act through different mechanisms and by a non-specific manner, each one shows a certain preference for specific cell subpopulations, depending on their cell size and their reactivity to isolectin B4. Our results support the idea that the biophysical properties that result from the interactions that arise in the membranes are part of the mechanotransduction process.

cGMP and cyclic nucleotide-gated channels participate in mouse sperm capacitation.

During capacitation of mammalian sperm intracellular [Ca(2+)] and cyclic nucleotides increase, suggesting that CNG channels play a role in the physiology of sperm. Here we study the effect of capacitation, 8Br-cAMP (8-bromoadenosine 3',5'-cyclic monophosphate) and 8Br-cGMP (8-bromoguanosine 3',5'-cyclic monophosphate) on the macroscopic ionic currents of mouse sperm, finding the existence of different populations of sperm, in terms of the recorded current and its response to cyclic nucleotides. Our results show that capacitation and cyclic nucleotides increase the ionic current, having a differential sensitivity to cGMP (cyclic guanosine monophosphate) and cAMP (cyclic adenosine monophosphate). Using a specific inhibitor we determine the contribution of CNG channels to macroscopic current and capacitation.