Transient outward current (I(A)) in clonal anterior pituitary cells: Blockade by aminopyridine analogs

Whole cell voltage-clamp recordings from GH₃ cells, a clonal cell line derived from a rat anterior pituitary tumor, demonstrated a rapidly activating and inactivating ('transient') voltage-dependent outward current. This current, referred to as I(A), was elicited by step depolarization from holding potentials negative to -50 mV, showed strong outward rectification at potentials positive to -30 mV, and exhibited steady state inactivation with V(1/2) near -64 mV. The current rose to a peak within < 10-20 ms following depolarization and decayed in two exponential phases, I(Af) and I(As), with time constants of 30-50 and 500-700 ms, respectively. Both I(A) components exhibited similar voltage dependencies for activation and inactivation. Aminopyridines (2 μmol/l-5 mmol/l) produced a dose-dependent, reversible blockade of I(A) (70% inhibition at 0.5 to 2 mmol/l) with the following rank order of potencies: 4-aminopyridine > 3,4-diaminopyridine = 3-aminopyridine > 2-aminopyridine. These drugs reduced the peak conductance of I(A), and produced complex effects on its time-dependent decay. With submaximal degrees of block, there was an increase in the inactivation rate, suggesting that open channels are preferentially blocked by the drugs. It is concluded that GH₃ pituitary cells possess an aminopyridine-sensitive transient outward current comparable to the A-current in neural cells. However, this cell line is unusual in that it expresses both rapidly and slowly decaying A-current components.