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, I(K1), 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-mu-M)] and 4-aminopyridine (4-AP, 40-mu-M). In the absence of intracellular Ca2+ buffering, the amplitude of I(K1) was both larger and dependent on holding potential, as expected for a Ca2+-dependent current. Replacement of [Ca2+]o by Co2+ reduced I(K1), although the addition of Cd2+ to Ca2+ -containing solutions had no effect. 3. The second component, I(K2), 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 I(K)2 were analogous to (but much slower than) those of I(A) in that both currents displayed voltage-dependent activation and voltage-independent inactivation. I(K2) was not reduced by the addition of Cd2+ to Ca2+ -containing solutions or by replacement of Ca2+ by Co2+. 4. I(K2) had a more depolarized activation threshold than I(A) and attained peak amplitude with a latency of approximately 100 ms at room temperature. I(K2) decay was nonexponential and could be described as the sum of two components with time constants (tau) near 1 and 10 s. 5. I(K2) 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 I(K2) varies in availability across a broad voltage range between - 100 and -20 mV. 6. Activation kinetics of I(K2) 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 I(K2), with temperature coefficient (Q10) values near 3 for activation and inactivation. Heating increased the amplitude of I(K2) with a Q10 value near 2. 7. Prolonged near-threshold depolarizing stimuli in RNs can activate I(K2), which initially inhibits spike firing. However, maintained stimulation will cause inactivation of I(K2), with an accompanying gradual depolarization that can eventually reach spike threshold. Therefore one function of I(K2) may be to cause delayed and/or accelerating spike firing in response to sustained depolarizing stimuli, allowing RNs to alter their integrating response to afferent inputs over periods of several seconds.