Small cell lung carcinoma (SCLC) is a very aggressive form of neuroendocrine lung tumor often associated with tobacco abuse. SCLC is composed of secretory cells that express a whole set of plasma membrane ion channels and receptors controlling cell excitability and the consequent Ca2+-dependent release of several hormones and transmitters. Some of the released hormones, including serotonin (5HT), act as autocrine growth factors. 1, 2 Therefore, the study of the properties of the ion channels and receptors expressed by these cells can lead to a possible pharmacological control of cell proliferation itself. Furthermore, the “inappropriate” expression of these membrane molecules on the growing SCLC causes an autoimmune response that, on the one hand, could be crucial for the inhibition of cell growth, but, on the other hand, could cause specific “paraneoplastic” disorders, caused by the cross-reactivity of these anti-SCLC antibodies with similar molecules expressed by the normal tissues, neurons in particular.

We will summarize in this paper some recent results that we obtained on the presence and function of nicotinic acetylcholine receptors (nAChRs) and voltage-operated calcium channels (VOCCs) in SCLC cells; we will describe some forms of modulation of these ion channels and their involvement as autoantigens in “paraneoplastic” disorders such as the Lambert-Eaton myasthenic syndrome (LEMS).