title: Mitogens and oncogenes can block the induction of specific voltage-gated ion channels.
abstract: The mechanisms underlying the ontogeny of voltage-gated ion channels in muscle are unknown. Whether expression of voltage-gated channels is dependent on mitogen withdrawal and growth arrest, as is generally true for the induction of muscle-specific gene products, was investigated in the BC3H1 muscle cell line by patch-clamp techniques. Differentiated BC3H1 myocytes expressed functional Ca2+ and Na+ channels that correspond to those found in T tubules of skeletal muscle. However, Ca2+ and Na+ channels were first detected after about 5 days of mitogen withdrawal. In order to test whether cellular oncogenes, as surrogates for exogenous growth factors, could prevent the expression of ion channels whose induction was contingent on mitogen withdrawal, BC3H1 cells were modified by stable transfection with oncogene expression vectors. Expression vectors containing v-erbB, or c-myc under the control of the SV40 promoter, delayed but did not prevent the appearance of functional Ca2+ and Na+ channels. In contrast, transfection with a Val12 c-H-ras vector, or cotransfection of c-myc together with v-erbB, suppressed the formation of functional Ca2+ and Na+ channels for greater than or equal to 4 weeks. Potassium channels were affected neither by mitogenic medium nor by transfected oncogenes. Thus, the selective effects of certain oncogenes on ion channel induction corresponded to the suppressive effects of mitogenic medium.
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004553:Electric Conductivity; D006133:Growth Substances / Q000502:physiology; D007473:Ion Channels / Q000502:physiology*; D008934:Mitogens / Q000494:pharmacology*; D009132:Muscles / Q000502:physiology*; D009857:Oncogenes; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014162:Transfection
chemical_list: D006133:Growth Substances; D007473:Ion Channels; D008934:Mitogens; D012964:Sodium; D011188:Potassium; D002118:Calcium