Phenytoin partially antagonized L-type Ca²⁺ current in glucagon-secreting tumor cells (ITC-1)

Summary

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°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 α₂ cells. Both currents were augmented by equimolar substitution of Ca²⁺ with Ba²⁺ and completely abolished by adding 1 μM 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 μM. The residual component of the L-type current was completely abolished by adding nifedipine.