Inherent pacemaker function of duodenal GIST.
Gastrointestinal stromal tumours (GIST) are thought to derive from interstitial cells of Cajal (ICCs), which are putative pacemaker cells for gut motility. Isolated cells were obtained by enzymatic treatment of human duodenum GIST tissue having a frequent gain-of-function gene mutation. After cell culturing, c-Kit immunoreactivity was preserved and the cells developed long processes. Whole cell patch clamp recordings revealed voltage-dependent outward currents, without transient inward currents. Intracellular Ca(2+) measurements showed oscillation-like spontaneous activity in some GIST cells. RT-PCR revealed expression of ion channels (Kv1.1, Kv1.6 and KCNH2; IP3R1, and IP3R2; TRPC1, 3, 6 and 7; Cx43), which have been suggested to play important roles in pacemaker activity. However, SCN5A, a TTX-resistant Na(+) channel known to be expressed in human ICCs, was below detectable levels. These data suggest that GIST cells appear to preserve some, but not all ionic mechanisms underlying pacemaker activity in ICC.
Furuzono
Shinji
S
Department of Cell Physiology, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan.
Ohya
Susumu
S
Inoue
Soichiro
S
Nakao
Akimasa
A
Imaizumi
Yuji
Y
Nakayama
Shinsuke
S
D002462:Cell Membrane / Q000502:physiology; D018076:DNA, Complementary / Q000378:metabolism; D004379:Duodenal Neoplasms / Q000503:physiopathology*; D017629:Gap Junctions / Q000378:metabolism; D046152:Gastrointestinal Stromal Tumors / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D018076:DNA, Complementary; D012334:RNA, Neoplasm