Slow inactivation of a TEA-sensitive K current in acutely isolated rat thalamic relay neurons

1. Voltage-gated K currents were studied in relay neurons (RNs) acutely isolated from somatosensory (VB) thalamus of 7- to 14-day-old rats. In addition to a rapidly activated, transient outward current, IA, depolarizations activated slower K+ currents, which were isolated through the use of appropriate ionic and pharmacological conditions and measured via whole-cell voltage-clamp. 2. At least two slow components of outward current were observed, both of which were sensitive to changes in [K+]o, as expected for K conductances. The first, IK1, had an amplitude that was insensitive to holding potential and a relatively small conductance of 150 pS/pF. It was blocked by submillimolar levels of tetraethylammonium [TEA, 50%-inhibitory concentration (IC50 = 30 microM)] and 4-aminopyridine (4-AP, 40 microM). In the absence of intracellular Ca2+ buffering, the amplitude of IK1 was both larger and dependent on holding potential, as expected for a Ca(2+)-dependent current. Replacement of [Ca2+]o by Co2+ reduced IK1, although the addition of Cd2+ to Ca(2+)-containing solutions had no effect. 3. The second component, IK2, had a normalized conductance of 2.0 nS/pF and was blocked by millimolar concentrations of TEA (IC50 = 4 mM) but not by 4AP. The kinetics of IK2 were analogous to (but much slower than) those of IA in that both currents displayed voltage-dependent activation and voltage-independent inactivation. IK2 was not reduced by the addition of Cd2+ to Ca(2+)-containing solutions or by replacement of Ca2+ by Co2+. 4. IK2 had a more depolarized activation threshold than IA and attained peak amplitude with a latency of approximately 100 ms at room temperature. IK2 decay was nonexponential and could be described as the sum of two components with time constants (tau) near 1 and 10 s. 5. IK2 was one-half steady-state inactivated at a membrane potential of -63 mV, near the normal resting potential for these cells. The slope factor of the Boltzman function describing steady-state inactivation was 13 mV-1, which indicates that IK2 varies in availability across a broad voltage range between -100 and -20 mV. 6. Activation kinetics of IK2 were voltage dependent, with peak latency shifting from 300 to 50 ms in the voltage range -50 to +30 mV. Deinactivation and deactivation were also voltage dependent, in contrast to inactivation, which showed little dependence on membrane potential. Increase in temperature sped the kinetics of IK2, with temperature coefficient (Q10) values near 3 for activation and inactivation. Heating increased the amplitude of IK2 with a Q10 value near 2.(ABSTRACT TRUNCATED AT 400 WORDS)