Ion channel phenotype of melanoma cell lines

Melanoma cells are transformed melanocytes of neural crest origin. K+ channel blockers have been reported to inhibit melanoma cell proliferation. We used whole-cell recording to characterize ion channels in four different human melanoma cell lines (C8161, C832C, C8146, and SK28). Protocols were used to identify voltage-gated (K-V), Ca2+-activated (K-Ca), and inwardly rectifying (K-IR) K+ channels; swelling-sensitive Cl- channels (Cl-swell); voltage-gated Ca2+ channels (Ca-V) and Ca2+ channels activated by depletion of intracellular Ca2+ stores (CRAC); and voltage-gated Na+ channels (Na-V). The presence of Ca2+ channels activated by intracellular store depletion was further tested using thapsigargin to elicit a rise in [Ca2+](i). The expression of K+ channels varied widely between different cell lines and was also influenced by culture conditions. K-IR channels were found in all cell lines, but with varying abundance. Whole-cell conductance levels for K-IR differed between C8161 (100 pS/pF) and SK28 (360 pS/pF). K-Ca channels in C8161 cells were blocked by 10 nM apamin, but were unaffected by charybdotoxin (CTX). K-Ca channels in C8146 and SK28 cells were sensitive to CTX (K-d=4 nM), but were unaffected by apamin. K-V channels, found only in C8146 cells, activated at similar to-30 mV and showed use dependence. All melanoma lines tested expressed CRAC channels and a novel Cl-swell channel. Cl-swell current developed at 30 pS/sec when the cells were bathed in 80% Ringer solution, and was strongly outwardly rectifying (4:1 in symmetrical Cl-). We conclude that different melanoma cell lines express a diversity of ion channel types.