1. We describe three outward K+ current components in acutely dissociated neurons from rat sensorimotor cortex on the basis of inactivation kinetics and voltage dependence. 2. The fast A current (I(Af)) was completely inactivated at -40 mV and half-inactivated at -52 mV. It activated [time to peak (TTP) 8 ms at -10 mV] and was inactivated (tau(inact) = 12 ms at -10 mV) rapidly. Recovery from inactivation had a time constant of approximately 80 ms at -100 mV. It was insensitive to tetraethyl ammonium (TEA) and dendrotoxin but was blocked by 4-aminopyridine (4-AP, IC50 = 1 mM). 3. The slowly inactivating current (I(Ks)) was the largest current seen in acutely dissociated adult neurons. It was completely inactivated at -40 mV, half-inactivated at -98 mV, and was kinetically slower (TTP = 130 ms at -10 mV; tau(inact) = 293 ms at -10 mV) than the fast A current. Deactivation tails were fit with the sum of two exponentials with time constants of 2-10 and 15-40 ms. I(KS) recovered from inactivation with a time constant of approximately 1,200 ms at -100 mV. 4. There were two components that inactivated with even slower kinetics. The very slowly inactivating current (I(KSS)) was operationally defined as the current remaining after a 5-s hold at -40 mV. One component inactivated with a time constant of 1,927 ms at -10 mV. The other component showed no inactivation over a 5-s test command, but in 40- to 50-s steps to -10 mV, inactivated with a tau of approximately 20 s. The very slowly inactivating current activated with similar kinetics to I(KS) (TTP = 121 ms at -10 mV), and two deactivation tails, with kinetics similar to those after the -100 mV prepulse, were observed after holding at -40 mV. 5. Both I(KS) and I(KSS) were sensitive to TEA. Seventy-six percent (76%) of I(KSS) was blocked by 30 mM TEA. Two components to the TEA block were present for I(KSS), with IC50s of 88 muM (67% of blockable current) and 7 mM (33%). Seventy percent (70%) of I(KS) was blocked by 30 mM TEA. For the I(KS) current, there were also two effective concentrations, with IC50s of 8 muM (21% of blockable current) and 3 mM (79%). 6. I(KS) and I(KSS) were also sensitive to 4-AP. Seventy-six percent (76%) of I(KSS) was blocked by 3-5 mM 4-AP. I(KSS) exhibited two components of 4-AP block. The high-affinity component had an IC50 of 90 muM (66% of blockable current), and the low-affinity component had an IC50 of 7 mM (34% of current). Only 24% of I(KS) was sensitive to 3-5 mM 4-AP. This block was well fit by a single IC50 of 92 muM. 7. I(KS) and I(KSS) were also dendrotoxin sensitive. I(KSS) was blocked by 100 nM dendrotoxin (100% block). I(KSS) exhibited two components of dendrotoxin block, with IC50s of 266 pM (46% of current) and 27 nM (54%). Only 36% of I(KS) was blocked by 100 nM dendrotoxin. This block had two components with IC50s of 146 pM (29% of blockable current) and 10.4 nM (71% of current). 8. A model is discussed in which the voltage-gated K+ currents are represented by four channel types: fast A (A(f)), slowly inactivating (K1), and two very slowly inactivating types (K2 and K3).
