A fast, transient K+ current in neurohypophysial nerve terminals of the rat.
1. Nerve terminals of the rat posterior pituitary were acutely dissociated and identified using a combination of morphological and immunohistochemical techniques. Macroscopic terminal membrane currents and voltages were studied using the whole-cell patch clamp technique. 2. In physiological solutions, depolarizing voltage clamp steps, from a holding potential (-80 mV) similar to the normal terminal resting potential, elicited a fast, inward followed by a fast, transient, outward current. 3. The threshold of activation for the outward current was -60 mV. The outward current quickly reached a peak and then decayed more slowly. The decay was fitted by two exponentials with time constants of 21 +/- 2.9 and 143 +/- 36 ms. These decay constants did not show a dependence on voltage. The time to peak of the outward current decreased and the amplitude increased with increasingly depolarized potential steps. 4. The outward current was blocked by the substitution of K+ with Cs+ and its reversal potential was consistent with a potassium current. 5. The transient outward current showed steady-state inactivation at more depolarized (than -80 mV) holding potentials with 50% inactivation occurring at -47.9 mV. The time course of recovery from inactivation was complex with full recovery taking greater than 16 s. 6. 4-Aminopyridine (4-AP) blocked the transient outward current in a dose-dependent manner (approximately IC50 = 3 mM), while charybdotoxin (4 micrograms/ml) and tetraethylammonium (100 mM) had no effect on the current amplitude. 7. Lowering external [Ca2+] had no effect on the fast, transient outward current nor did the calcium channel blocker Cd2+ (2 mM). 8. The neurohypophysial outward current reported here corresponds most closely to IA, and not to the delayed rectifier or Ca2(+)-activated K+ currents. Neurohypophysial IA, however, appears to be different from the outward currents found in the cell bodies in the hypothalamus which project their axons to the posterior pituitary. 9. Under current clamp, evoked action potential duration increased (122%) upon application of 5 mM-4-AP, indicating that IA is involved in neurohypophysial spike repolarization. 10. The existence of this current could help explain why maximal peptide release only occurs in response to bursts of electrical activity invading the nerve terminals.
Thorn
P J
PJ
Worcester Foundation for Experimental Biology, Neurobiology Division, Shrewsbury, MA 01545.
Wang
X M
XM
Lemos
J R
JR
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009411:Nerve Endings / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000294:innervation*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium