Modulation of the excitability of stellate neurons in the ventral cochlear nucleus of mice by TRPM2 channels.

Oxidative stress-induced Ca2+ permeable transient receptor potential melastatin 2 (TRPM2) channels are expressed at high levels in the brain, appear to link neuronal excitability to cellular metabolism, and are involved in the pathogenesis of neurodegenerative disorders. We aimed to study the electrophysiological properties of TRPM2 channels in stellate cells of the mouse ventral cochlear nucleus (VCN) using molecular, immunohistochemical and electrophysiological approaches. In the present study, the real time PCR analysis revealed the presence of the TRPM2 mRNA in the mouse VCN tissue. Cell bodies of stellate cells were moderately labeled with TRPM2 antibodies using immunohistochemical staining. Stellate cells were sensitive to intracellular ADP-ribose (ADPR), a TRPM2 agonist. Upon the application of ADPR, the resting membrane potential of the stellate cells was significantly depolarized, shifting from -61.2 ± 0.9 mV to -57.0 ± 0.8 mV (P < 0.001; n = 21), and the firing rate significantly increased (P < 0.001, n = 6). When the pipette solution contained ADPR (300 µM) and the TRPM2 antagonists flufenamic acid (FFA) (100 µM), N-(p-amylcinnamoyl) anthranilic acid (ACA) (50 µM) and 8-bromo-cADP-Ribose (8-Br-cADPR) (50 µM), the membrane potential shifted in a hyperpolarizing direction. ADPR did not significantly change the resting membrane potential and action potential firing rate of stellate cells from TRPM2-/- mice. In conclusion, the results obtained using these molecular, immunohistochemical and electrophysiological approaches reveal the expression of functional TRPM2 channels in stellate neurons of the mouse VCN. TRPM2 might exert a significant modulatory effect on setting the level of resting excitability.

TRPM2 mediates distruption of autophagy machinery and correlates with the grade level in prostate cancer.

PURPOSE: Transient receptor potential melastatin 2 (TRPM2), a calcium-permeable ion channel, is shown as a prognostic marker candidate in prostate cancer (PCa) and an important regulator of autophagy. We aimed to determine the changes in TRPM2 and autophagic-apoptotic gene expression levels in human prostate adenocarcinomas, and to investigate the affect of TRPM2 on autophagic pathways in PC-3 cell line. METHODS: Human prostate tissues were classified considering the grade levels and were divided into the control, BPH, and grade 1-5 groups. mRNA expression levels of genes were determined by qPCR. In addition, TRPM2 was evaluated immunohistochemically for each group. In PC-3 cell line, TRPM2 was silenced through siRNA transfection, and autophagy induction was analyzed by acridine orange (AO) staining. RESULTS: The qPCR and immunoreactivity results showed that the increased TRPM2 expression levels in human PCa samples were paralleled with higher grade levels. The autophagic-apoptotic gene expressions showed high variability in different grade levels. Also, silencing TRPM2 in PC-3 cells altered autophagic gene expressions and caused autophagy induction according to the AO staining results. CONCLUSION: We showed that the autophagy-TRPM2 association may take place in the molecular basis of PCa and accordingly this connection may be targeted as a new therapeutic approach in PCa.

The increased expression of Piezo1 and Piezo2 ion channels in human and mouse bladder carcinoma.

BACKGROUND: Piezo1/2, a mechanically activated ion channel, is believed to play an important role in bladder carcinogenesis process. Piezo1/2 expression has not been previously reported in urinary bladder carcinoma, and little is known about its significance in bladder carcinogenesis. OBJECTIVES: In our study, we aimed to evaluate the Piezo1 and Piezo2 expression as developmental in mouse bladder tissue and bladder cancer tissue of mice and humans. MATERIAL AND METHODS: The detection of developmental expression was performed on P0-P90 days in bladder tissue of Balb/c strain mice. Mice were divided into bladder cancer (n = 40) and control groups (n = 10). Bladder cancer in mice was created by using N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In the study, 60 human subjects were included, whose normal tissues were used as controls. After the histopathological evaluation, the expression of Piezo1/2 genes was examined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry in tumor and normal tissues. RESULTS: In developmental period of the mice, Piezo1 expression increased on days 21 and 90, whereas Piezo2 expression increased on day 7 and decreased on day 90 in mouse bladder tissues. There was a significant increase in the expression of Piezo1/2 in both cancer groups compared to the control group. Piezo1 expression was significantly increased at tumor size, stage and grade. Piezo2 expression was upregulated in high grade tumors in human subjects. CONCLUSIONS: The developmental changes of Piezo expression on specific days demonstrate the role of these channels in bladder cancer development. The dysfunction of Piezo1/2 expression may contribute to the carcinogenesis of bladder cancer by causing proliferative changes and angiogenesis. The expression of Piezo1/2 can provide new prognostic information for disease progression.

Ion channel gene expressions in infertile men: A case-control study.

BACKGROUND: Infertility is described as not receiving pregnancy despite unprotected and regular sexual intercourse in a 1 yr period. It is detected by 15% of the couples. Male and female factor in the etiology may be detected in similar rates. OBJECTIVE: The present study aims to investigate ion channel gene expression in semen samples of infertile male compared with fertile men. MATERIALS AND METHODS: A total of 150 men who applied to the urology clinic due to infertility were divided into five equal groups: asthenozoospermia, oligozoospermia, oligoasthenoteratozoospermia, teratozoospermia, and normozoospermia (control). All paticipants were evaluated with Cation Channel Spermia (CatSper) 1, 2, 3, 4, Proton Voltage Gated Ion Channel1 (Hv1), Potassium Channel Subfamily U1 (KCNU1), and transmembrane protein (TMEM16A) gene expression in semen samples. RESULTS: "CatSper1, 4, HV1, KCNU1, and TMEM16A gene expression were detected higher in the oligozoospermia group compared to the controls. CatSper1, 2, 3, 4, KCNU1, and TMEM16A gene expression in the asthenozoospermia group and CatSper1, 2, 3, 4, KCNU1, and TMEM16A gene expression in the teratozoospermia group were detected lower compared to the controls. CatSper1, 4, HV1, and TMEM16A gen expression were higher in the oligoasthenoteratozoospermia men than the controls while CatSper3 gen expression was detected as lower." CONCLUSION: It was detected that these ion channels have an effect on sperm progressive motility and morphology. It may be considered that mutations in these ion channels may result in infertility.