KCa2.3 channel-dependent hyperpolarization increases melanoma cell motility.
Cell migration and invasion are required for tumour cells to spread from the primary tumour bed so as to form secondary tumours at distant sites. We report evidence of an unusual expression of KCa2.3 (SK3) protein in melanoma cell lines but not in normal melanocytes. Knockdown of the KCa2.3 channel led to plasma membrane depolarization, decreased 2D and 3D cell motility. Conversely, enforced production of KCa2.3 protein in KCa2.3 non-expressing cells led to the plasma membrane becoming hyperpolarized, and enhanced cell motility. In contrast, KCa3.1 channels had no effect on cell motility despite an active role in regulating membrane potential. Our data also suggest that membrane hyperpolarization increases melanoma cell motility and that this occurs through the KCa2.3 channel. Our findings reveal a previously unknown function of the KCa2.3 channel, and suggest that the KCa2.3 channel might be the only member of the Ca(2+)-activated K(+) channel family involved in melanoma cell motility pathways.
Chantome
Aurelie
A
Inserm, U921, F-37032 Tours, France.
Girault
Alban
A
Potier
Marie
M
Collin
Christine
C
Vaudin
Pascal
P
Pagès
Jean-Christophe
JC
Vandier
Christophe
C
Joulin
Virginie
V
D001030:Apamin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D014162:Transfection
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C406328:KCNN3 protein, human; C496923:KCNN4 protein, human; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D016372:RNA, Antisense; D051640:Small-Conductance Calcium-Activated Potassium Channels; C411671:TRAM 34; D001030:Apamin; D003022:Clotrimazole