Transient outward current (IA) 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 IA, 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 less than 10-20 ms following depolarization and decayed in two exponential phases, IAf and IAs, with time constants of 30-50 and 500-700 ms, respectively. Both IA components exhibited similar voltage dependencies for activation and inactivation. Aminopyridines (2 mumol/1-5 mmol/l) produced a dose dependent, reversible blockade of IA (70% inhibition at 0.5 to 2 mmol/l) with the following rank order of potencies: 4-aminopyridine greater than 3,4-diaminopyridine = 3-aminopyridine greater than 2-aminopyridine. These drugs reduced the peak conductance of IA, 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.