Expression of the H-ras oncogene induces potassium conductance and neuron-specific potassium channel mRNAs in the AtT20 cell line.
Expression of the EJ-ras oncogene in the AtT20 cell line results in several changes in their properties that correspond to a switch of these anterior pituitary-derived cells to a more neuronlike phenotype. The width of action potentials following transfection with ras is reduced 20-fold from over 200 msec in control AtT20 cells to less than 10 msec in ras-transfected cells. This is associated with a two- to threefold increase in the density of voltage-dependent potassium currents. In addition, the rate of inactivation of these currents is decreased approximately twofold in ras-transfected cells. At least part of the change in potassium current may be due to differential expression of potassium channel mRNAs. In the ras-transfected cells, mRNA species were detected using a probe for the voltage-dependent potassium channels, Kv4, a species that appears to be uniquely expressed in the nervous system, and NGK2, an alternatively spliced product transcribed from the same gene. These mRNAs are not detected in control AtT20 cells. The results suggest that the ras protein modulates the phenotype of excitable cells by influencing the expression of specific potassium channels and thereby altering the density and types of channels in the plasma membrane.
Hemmick
L M
LM
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Perney
T M
TM
Flamm
R E
RE
Kaczmarek
L K
LK
Birnberg
N C
NC
D004553:Electric Conductivity; D004594:Electrophysiology; D015870:Gene Expression; D011905:Genes, ras; D009474:Neurons / Q000378:metabolism*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D012333:RNA, Messenger; D011188:Potassium