Three Kinetically Distinct Ca²⁺-Independent Depolarization-Activated K⁺ Currents in Callosal-Projecting Rat Visual Cortical Neurons

Abstract

Three kinetically distinct Ca 2+ -independent depolarization-activated K + currents in callosalprojecting rat visual cortical neurons. J. Neurophysiol. 78: 2309Neurophysiol. 78: -2320Neurophysiol. 78: , 1997. Whole cell, Ca 2+ -independent, depolarization-activated K + currents were characterized in identified callosalprojecting (CP) neurons isolated from postnatal day 7-16 rat primary visual cortex. CP neurons were identified in vitro after in vivo retrograde labeling with fluorescently tagged latex microbeads. During brief (160-ms) depolarizing voltage steps to potentials between −50 and +60 mV, outward K + currents in these cells activate rapidly and inactivate to varying degrees. Three distinct K + currents were separated based on differential sensitivity to 4-aminopyridine (4-AP); these are referred to here as I A , I D , and I K , because their properties are similar (but not identical) K + currents termed I A , I D , and I K in other cells. The current sensitive to high (≥ 100 μM) concentrations of 4-AP (I A ) activates and inactivates rapidly; the current blocked completely by low (≤ 50 μM) 4-AP (I D ) activates rapidly and inactivates slowly. A slowly activating, slowly inactivating current (I K ) remains in the presence of 5 mM 4-AP. I A , I D , and I K also were separated and characterized in experiments that did not rely on the use of 4-AP. All CP cells express all three K + current types, although the relative densities of I A , I D , and I K vary among cells. The experiments here also have revealed that I A , I D , and I K display similar voltage dependences of activation and steady state inactivation, whereas the kinetic properties of the currents are distinct. At + 30 mV, for example, mean ± SD activation τs are 0.83 ± 0.24 ms for I A , 1.74 ± 0.49 ms for I D , and 14.7 ± 4.0 ms for I K . Mean ± SD inactivation τs for I A and I D are 26 ± 7 ms and 569 ± 143 ms, respectively. Inactivation of I K is biexponential with mean ± SD inactivation time constants of 475 ± 232 ms and 3,128 ± 1,328 ms; ∼20% of the 4-AP-insensitive current is noninactivating. For all three components, activation is voltage dependent, increasing with increasing depolarization, whereas inactivation is voltage independent. Both I A and I K recover rapidly from steady state inactivation with mean ± SD recovery time constants of 38 ± 7 ms and 79 ± 26 ms, respectively; I D recovers an order of magnitude more slowly (588 ± 274 ms). The properties of I A , I D , and I K in CP neurons are compared with those of similar currents described previously in other mammalian central neurons and, in the accompanying paper, the roles of these conductances in regulating the firing properties of CP neurons are explored.

State-Dependent Enhancement of Subthreshold A-Type Potassium Current by 4-Aminopyridine in Tuberomammillary Nucleus Neurons

“…2C). These results are consistent with those in other mammalian neurons showing low sensitivity of somatodendritic A-type potassium current to external TEA and moderate sensitivity to 4-AP (Segal et al, 1984;Huguenard et al, 1991;Bouskila and Dudek, 1995;Klee et al, 1995;Locke et al, 1997;Song et al, 1998). The high TEA sensitivity of the steadystate current activated by stronger depolarizations suggests that this component of current originates from different channel types than those underlying the transient current.…”

“…Somatodendritic I A is often distinguished from other components of potassium current by its pharmacology. Somatodendritic I A is relatively resistant to external tetraethylammonium (TEA) (half-block, Ͼ100 mM) and moderately sensitive to 4-aminopyridine (4-AP) with a typical half-blocking concentration of ϳ1 mM (Segal et al, 1984;Zbicz and Weight, 1985;Huguenard et al, 1991;Klee et al, 1995;Locke et al, 1997;Song et al, 1998) (for review, see Song, 2002;Jerng et al, 2004b). Thus, the functional roles of I A are often studied by examining the effect of 3-10 mM 4-AP.…”

Action potentials reliably invade axonal arbors of rat neocortical neurons

“…Previous studies have reported 4-aminopyridine-sensitive currents in rat neocortical pyramidal cells (see ref. 33 and citations therein). Consistent with these studies, in our preparation, application of 4-aminopyridine (100 M) reduced a depolarization-activated hyperpolarizing current (n ϭ 2).…”

Kv4.3-Mediated A-Type K+Currents Underlie Rhythmic Activity in Hippocampal Interneurons

“…In hippocampal interneurons, MPOs are prevented by Ba 2ϩ and 4-aminopyridine (4-AP) but not by tetraethylammonium (TEA) (Chapman and Lacaille, 1999a). This pharmacological profile suggests that transient A-type K ϩ currents or dendrotoxinsensitive K ϩ currents (I D ) may be involved in MPO generation (Rudy, 1988;Hurst et al 1995;Locke and Nerbonne, 1997;Coetzee et al 1999;Shi et al 2000). Activation of MPOs at subthreshold membrane potentials (Chapman and Lacaille, 1999a) is also consistent with a potentially important role of these currents (Coetzee et al, 1999;Lien et al, 2002).…”