Sodium channel TRPM4 and sodium/calcium exchangers (NCX) cooperate in the control of Ca2+-induced mucin secretion from goblet cells

Abstract

2 The abbreviations used are: MUC2, mucin-2; CF, cystic fibrosis; MUC5AC, mucin-5AC; NCX, sodium-calcium exchanger; NHBE, normal human bronchial epithelial cells; PMA, phorbol 12-myristate 13-acetate; TRPM4, transient receptor potential cation channel subfamily M member 4; TRPM5, transient receptor potential cation channel subfamily M member 5; MARCKS, myristoylated alanine-rich protein kinase C substrate; PM, plasma membrane; SOCE, store-operated calcium entry; TG, thapsigargin; ALI, air-liquid interface; IL-13, interleukin-13; ER, endoplasmic reticulum; DAPI, 4Ј,6-diamidino-2-phenylindole; AUC, area under the curve; PKC, protein kinase C, SNARE, soluble NSF attachment protein receptor(s); IP 3 , inositol 1,4,5-trisphosphate; shRNA, short hairpin RNA; qPCR, quantitative PCR.

Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells

“…Furthermore, earlier work demonstrated that H 2 S release was able to increase the expression levels of NCX1 [ 100 ], the main NCX isoform expressed in CRC cells [ 20 ]. It is, therefore, possible to conclude that TRPV1 and NCX may by physically coupled in primary mCRC cells, as also described for TRP Melastatin 4 [ 101 ] and TRP Canonical 6 [ 102 ]. This feature might contribute to explaining why capsaicin- and NaHS-evoked extracellular Ca 2+ entry is larger in mCRC cells although TRPV1 protein expression was similar in mCRC and non-neoplastic cells.…”

TRPM4 in Cancer—A New Potential Drug Target

“…Dysregulations of TRPM4 by either altered expression levels or mutations have been linked to several pathological conditions, including cardiac disorders [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], immune diseases [ 13 , 14 , 25 , 26 ], and neurological disorders [ 27 , 28 , 29 ]. In addition, TRPM4 was suggested to be an interesting pharmacological target for the treatment of mucus-related diseases, such as cystic fibrosis, as it was recently shown to be involved in goblet cell mucin secretion [ 30 ]. TRPM4 has been suggested to play a role in insulin secretion in pancreatic β-cells [ 31 ].…”

TRPM4 is highly expressed in human colorectal tumor buds and contributes to proliferation, cell cycle, and invasion of colorectal cancer cells

“…In CRC, TRPM4 mRNA expression is reported to be decreased (Sozucan et al , ) or not changed (Pérez‐Riesgo et al , ). It has also been suggested that TRPM4 may play a role in Ca 2+ ‐induced mucin secretion from goblet cells (Cantero‐Recasens et al , ). The role of TRPM4 in CRC pathophysiology has not been investigated.…”