Transient outward K+ currents in rat dissociated subfornical organ neurones and angiotensin II effects

Although angiotensin II inhibits transient outward K+ currents (I(A)s) in subfornical organ neurones, there is no evidence concerning which Kv channels are involved. We investigated I-A-generating Kv channels in dissociated rat subfornical organ neurones, using Molecular, electrophysiological and pharmacological techniques, and studied the effects of angiotensin II. Conventional RT-PCR showed the presence of mRNAs for channels of the Kv3.4, Kv1.4 and Kv4 families, which are capable of generating I(A)s. Tetraethylammonimn at I mm, which blocks Kv3 channel-derived currents, and blood-depressing substance-I, a Kv3.4-specific blocker, at 2 mu m suppressed the I-A-like component of whole-cell outward currents in some neurones. 4-Aminopyridine at 5 mm inhibited IAS in the presence of tetraethylammonium at 1 mm. Cd2+ at 300 mu m shifted the activation and inactivation curves of the 4-aminopyridine-sensitive and tetraethylammonium-resistant IAs positively. The tetraethylammonium-resistant IAS showed fast and slow components during the process of recovery from inactivation, but the slow component was not seen in all neurones. The time constant of the fast recovery component was less than 200 ms, while that of the slow recovery component was around 1 s. Using single-cell RT-PCR, mRNAs for Kv4.2 and Kv4.3L were detected frequently, but those for Kv1.4 and Kv3.4 were seen only rarely. Angiotensin II at 30 nm inhibited the fast recovery component of tetraethylammonium-resistant IAs in many neurones. These results suggest that the fast recovery component of the tetraethylammonium-resistant I-A in subfornical organ neurones depends upon Kv4, and that it can be modulated by angiotensin II.