Phenytoin partially antagonized L-type Ca2+ current in glucagon-secreting tumor cells (ITC-1).
Transmembrane Ca2+ currents were investigated by means of a whole-cell clamp technique in a hamster glucagon-secreting tumor cell line (ITC-1). Two types of Ca2+ current were identified in ITC-1 cells. The low-threshold and transient (T-type) current became detectable above the potential level around -60 mV and decayed rapidly with an inactivation time constant of 95 ms (at -40 mV and 23 degrees C), while the high-threshold and long-lasting (L-type) one was activated by depolarization more positive to -30 mV with non-inactivating kinetics. The voltage dependence and kinetics of these currents were identical to those reported in guinea-pig pancreatic alpha 2 cells. Both currents were augmented by equimolar substitution of Ca2+ with Ba2+ and completely abolished by adding 1 microM La3+. Phenytoin, a well known anti-epileptic drug and a postulated T-type specific Ca2+ current antagonist, surprisingly blocked the L-type current without affecting the T-type current in ITC-1 cells. While phenytoin antagonized the L-type Ba2+ current selectively, 60% of the current remained even in supramaximal concentration range over 500 microM. The residual component of the L-type current was completely abolished by adding nifedipine.
Miyazaki
T
T
Department of Physiology, Tokyo Medical College, Japan.
Hashiguchi
T
T
Hashiguchi
M
M
Sakai
S
S
Tosaka
T
T
Kanazawa
M
M
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects*; D006224:Cricetinae; D004594:Electrophysiology; D005934:Glucagon / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008647:Mesocricetus; D009543:Nifedipine / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D015220:Calcium Channels; D001464:Barium; D010672:Phenytoin; D007811:Lanthanum; D005934:Glucagon; D009543:Nifedipine; D002118:Calcium