KATP and TRPM2-like channels couple metabolic status to resting membrane potential of octopus neurons in the mouse ventral cochlear nucleus.

ATP-sensitive potassium (KATP) channels and transient receptor potential melastatin 2 (TRPM2) channels are commonly expressed both pre- and postsynaptically in the central nervous system (CNS). We hypothesized that KATP and TRPM2 may couple metabolic status to the resting membrane potential of octopus neurons of the mouse ventral cochlear nucleus (VCN). Therefore, we studied the expression of KATP channels and TRPM2 channels in octopus cells by immunohistochemical techniques and their contribution to neuronal electrical properties by the electrophysiological patch clamp technique. In immunohistochemical staining of octopus cells, labelling with Kir6.2 and SUR1 antibodies was strong, and labelling with the SUR2 antibody was moderate, but labelling with Kir6.1 was very weak. Octopus cells had intense staining with TRPM2 antibodies. In patch clamp recordings, bath application of KATP channel agonists H2O2 (880 µM), ATZ (1 mM), cromakalim (50 µM), diazoxide (200 µM), NNC 55-0118 and NN 414 separately resulted in hyperpolarizations of resting potential to different extents. Application of 8-Bro-cADPR (50 µM), a specific antagonist of TRPM2 channels, in the presence of H2O2 (880 µM) resulted in further hyperpolarization by approximately 1 mV. The amplitudes of H2O2-induced outward KATP currents and ADPR-induced inward currents were 206.1 ± 31.5 pA (n = 4) and 136.8 ± 22.4 pA, respectively, at rest. Their respective reversal potentials were -77 ± 2.6 mV (n = 3) and -6.3 ± 2.9 (n = 3) and -6.3 ± 2.9 (n = 3). In conclusion, octopus cells appear to possess both KATP channels and TRPM2-like channels. KATP might largely be constituted by SUR1-Kir6.2 subunits and SUR2-Kir6.2 subunits. Both KATP and TRPM2-like channels might have a modulatory action in setting the membrane potential.

Regular exercise, overweight/obesity and sedentary lifestyle cause adaptive changes in thiol-disulfide homeostasis.

Dynamic thiol-disulfide homeostasis is considered to have critical roles in maintenance of physiological functioning. We aimed to reveal whether there is any specific aberration in thiol-disulfide homeostasis in three distinct categories of individuals, including those who 1) exercise regularly (fitness group), 2) have a sedentary lifestyle (sedentary group) and 3) are overweight or obese (overweight/obese group). 72 male individuals were included in the study, 21 of whom were in fitness group, 28 of whom were overweight or obese and 23 of whom had a sedentary lifestyle. Plasma native thiol (-SH) and total thiol [(-SH) + (-S-S-)] levels were quantitatively determined. Total thiol levels in sedentary group were significantly lower than those in overweight/obese (p<0.05) and fitness groups (p<0.001). Also, disulfide values in fitness group were significantly higher than those in sedentary and overweight/obese groups (p<0.005, p<0.05). On the other hand, disulfide level, reduced and oxidized thiol ratios and oxidation/reduction ratio in fitness group differed significantly from the other groups (p<0.05). Thiol-disulfide homeostasis varies depending on lifestyle. The results of our study indicate that higher total thiol and disulfide levels are conspicuously distinctive features of thiol-disulfide homeostasis in individuals exercising regularly.