Journal of Neuroscience, Vol 15, 274-283, Copyright © 1995 by Society for Neuroscience
Expression and antibody inhibition of P-type calcium channels in human small-cell lung carcinoma cells
EL Barry, MP Viglione, YI Kim and SC Froehner
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755.
P-type channels, a recently described form of voltage-gated calcium
channels, are found in many central and peripheral neurons. In the present
study, a partial cDNA clone sharing extensive nucleotide identity with a
putative P-type voltage-gated calcium channel alpha 1 subunit was isolated
from a small-cell lung carcinoma (SCLC) cell line. Anti-peptide antibodies
generated to a unique acidic stretch in the IVS5-S6 linker region of the
putative SCLC P-type channel reacted specifically with a SCLC fusion
protein produced in bacteria and with a cell surface molecule in SCLC
cells. Calcium currents in SCLC cells, measured by whole-cell patch clamp,
were inhibited by these antibodies and by the P-type channel-specific toxin
omega-agatoxin IVA. The inhibitory effects of the antibody and the toxin
were not additive, consistent with their proposed action on the same type
of channel. These results provide evidence for the expression of P-type
calcium channels by SCLC cells. The expression of neuron-related molecules
by these cells is of particular interest because small-cell lung carcinoma
is frequently associated with paraneoplastic disorders affecting the
nervous system.