A rapidly activating type of outward rectifier K+ current and A-current in rat suprachiasmatic nucleus neurones.

Abstract

1. The properties of calcium-independent (i.e. persisting in the absence of external calcium) depolarization-activated potassium currents in suprachiasmatic nucleus (SCN) neurones (n = 75) were studied under voltage-clamp conditions with whole-cell patch-clamp recordings in rat hypothalamic slices (150-175 microns). 2. Two distinct types of potassium currents were found. One was a rapidly activating and slowly inactivating type of outward rectifier (named IK(FR) for fast rectifier potassium current), similar to a potassium current described in cardiac muscle, and the other was a transient A-current (IA). 3. The rates of activation and deactivation of IK(FR) were voltage dependent. Time constants of activation fitted to n4 kinetics and declined from 3.5 ms (at -20 mV) to 1.1 ms (at 60 mV). Inactivation had a biexponential time course with voltage-independent time constants of 0.3 s (minor component) and 3.0 s (major component) between 10 and 50 mV. IK(FR) was activated above -40 mV with a V1/2 (membrane potential at half-maximal activation) of 14 +/- 2 mV and slope factor of -17 +/- 1 mV reaching a conductance (not maximal) of 10.8 +/- 1.7 nS at 60 mV. Steady-state inactivation had a slope factor of 11 +/- 1 mV. 4. IK(FR) was highly selective for K+ (PNa/PK = 0.002). Tetraethylammonium (TEA) reduced IK(FR) reversibly (IC50 = 20 mM), while 4-aminopyridine (4-AP) at 10 mM had little effect. The remaining current in 30 mM TEA was similar to that in control conditions, indicating that TEA reduced IK(FR) rather than revealed an additional TEA-resistant current. 5. The rate of IA activation was voltage dependent with time to peak declining from 8.5 ms (at -40 mV) to 3.6 ms (at 60 mV). Inactivation had a biexponential time course with voltage-dependent and voltage-independent time constants. The two components were similar in amplitude. IA was activated above -60 mV, reaching a maximal conductance of 3.6 +/- 0.4 nS at above 20 mV. Steady-state inactivation was complete above -10 mV. Rates of onset of inactivation (at -40 mV) and recovery from inactivation (at -100 mV) were similar with time constants of 39 +/- 5 and 41 +/- 9 ms, respectively. 6. IK(FR) and IA were found in every neurone tested in the SCN and in all locations throughout the nucleus. The possible function of these currents is discussed, particularly in relation to the circadian rhythm of firing rate in the SCN.