MULTIPLE COMPONENTS OF VOLTAGE-DEPENDENT POTASSIUM CURRENT IN NORMAL RAT ANTERIOR-PITUITARY-CELLS

1. Voltage-dependent K+ currents were studied in normal rat anterior p ituitary cells using the patch-clamp technique. To obtain cultures enr iched for lactotrophs, density gradient centrifugation was performed o n pituitary cells isolated from lactating rats. 2. Depolarizations to about -30 mV from a holding potential of -80 mV activate a rapidly ina ctivating [time constant (tau) similar to 15-20 ms at -20 mV] K+ curre nt. This transient current activated at low voltages (termed I-A) is a bolished by 5 mM external 4-aminopyridine (4-AP) but is largely resist ant to external tetraethylammonium (TEA) (less than or equal to 30 mM) . 3. Recovery from inactivation of I-A is fast, with a tau of 100-200 ms at -80 mV. Deactivation is also fast (tau similar to 2.2 ms at -50 mV). The voltage of half-activation of I-A is approximately -20 mV. Th e current is completely inactivated at a holding potential of -40 mV. 4. Voltage-dependent K+ current activated by depolarizations from a ho lding potential of -40 mV was first detectable at about -20 mV (high v oltage-activated) and had a time course that varied among cells. 5. De activation of high voltage-activated K+ current was best described by the sum of two exponentials, with tau of about 3.7 and 30 ms at -50 mV . Both components reversed close to the equilibrium potential for K+ 6 . The amplitudes of the two tail currents were independent of each oth er when variable-duration commands were used to activate current. The amplitude of the fast component was largest with 10- to 20-ms commands to +40 mV and was reduced (less than or equal to 50%) with 136-ms com mands. The slow component amplitude reached a peak by 40 ms and remain ed constant for commands less than or equal to 136 ms at +40 mV. 7. Th e contribution of each component to the total high voltage-activated t ail current was variable among cells, with the amount of fast componen t correlating with the amount of inactivation produced by commands to +40 mV. 8. The two components of tail current activated by depolarizat ions from the -40 mV holding potential were abolished by external TEA (10 mM). 4-AP (5 mM externally) selectively abolished the fast compone nt of high voltage-activated tail current while only partially reducin g the slow component. 9. These results suggest that normal rat anterio r pituitary cells possess at least three distinct types of voltage-dep endent K+ current: a low voltage-activated, transient current (I-A) an d two high voltage-activated currents. The differential expression and /or modulation of these currents may be important in shaping the elect rophysiological response of pituitary cells to secretagogues.