Properties of two voltage-activated potassium currents in acutely isolated juvenile rat dentate gyrus granule cells

Abstract

1. The properties of outward currents were investigated in acutely isolated dentate gyrus granule cells at postnatal ages of day 5-7, 10-14, 18-24 (P5-7, P10-14, P18-24) and at adulthood (2-3 mo), with the use of the whole-cell patch-clamp technique. 2. Kinetic analysis and pharmacological properties showed that an A-type K+ current (IA) and a delayed rectifier current (IK) were present in these cells. 3. IA in P10-14 cells activated and inactivated rapidly with a decay time constant of 7.5 +/- 2.1 (SD) ms with command pulses to +30 mV. The removal of inactivation was monoexponential with a time constant of 23.1 ms (holding potential, -50 mV; conditioning voltage steps of varying duration to -110 mV). V 1/2 of the Boltzmann function describing steady-state inactivation was -65.1 +/- 1.8 mV with a slope factor of -6.0. IA was sensitive to 5 mM 4-aminopyridine (4-AP) but not to 10 mM tetraethylammonium (TEA). 4. IK in P10-14 cells displayed a voltage-dependent activation time constant (4.3 +/- 0.8 ms for command pulses to +30 mV and 16.2 +/- 2.4 for command pulses to -10 mV) and a double-exponential decay (time constants 194 +/- 21 and 1,625 +/- 254 ms). The rate constant of removal of inactivation was 332.1 ms. IK showed a reduction by 61.4 +/- 5.3% with 10 mM TEA and was partially blocked by 5 mM 4-AP in a subpopulation of cells. 5. Whereas IA remained stable over time, IK showed a substantial reduction of current amplitude by 67% after 30 min of cell perfusion through the patch pipette. The time course of this reduction was monoexponential with a time constant of 6.9 min and was partly due to a shift in V1/2 of the steady-state inactivation from -79.2 to -99.6 mV. 6. IA and IK remained stable with respect to kinetic properties during ontogenesis. However, the relative contribution and pharmacological properties of the investigated K+ currents varied with age. Although IA dominated in P5-7 cells, IK was prominent in most older cells. Five millimolars 4-AP reduced IA by 40.7 +/- 26.7% in P5-7 cells and blocked IA completely in 80% of investigated P10-14 cells. Similar changes were observed for the effects of 4-AP on IK (18.7% depression in the age group P5-8, 46.1% in the age group P10-14, and 45.7% in adult animals).

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

“…The slowly activating, TEA-sensitive K + current, which we have termed I K , in CP neurons closely resembles delayed rectifier type-currents described in neurons from rat thalamus , sensorimotor cortex (Foehring and Surmeier 1993;Hamill et al 1991), dentate gyrus (Beck et al 1992), lateral geniculate nucleus (LGN) (Budde et al 1992), hippocampus (Segal and Barker 1984), globus pallidus (Stefani et al 1995), and visual cortex (Albert and Nerbonne 1995;Foehring and Surmeier 1993) and from guinea pig hippocampus (Numann et al 1987). As in CP neurons, the threshold of I K activation in these cells is between −45 and −35 mV, i.e., positive to that of I A described in the same cells.…”

“…Rapidly activating and inactivating currents, similar to I A in CP neurons, have been characterized in neurons from rat hippocampus Segal and Barker 1984;Storm 1988), dentate gyrus (Beck et al 1992), neostriatum (Surmeier et al 1989), lateral geniculate nucleus (Budde et al 1992), thalamus , sensorimotor cortex (Foehring and Surmeier 1993;Hamill et al 1991), and visual cortex (Albert and Nerbonne 1995;Foehring and Surmeier 1993); the guinea pig (Numann et al 1987) and embryonic mouse (Wu and Barish 1992) hippocampus; and cat sensorimotor cortex (Spain et al 1991). The time-and voltage-dependent properties and the pharmacological sensitivities of the currents termed I A in these different preparations are similar.…”

“…In general, for example, I A activates rapidly at all test potentials, and activation is voltage dependent. Inactivation, although also rapid, is voltage independent (but see Beck et al 1992;Budde et al 1992;Spain et al 1991), and I A is blocked by millimolar concentrations of 4-AP (but see Spain et al 1991). In most cells, the threshold for I A activation lies between −65 and −50 mV, and steady state inactivation of I A is characterized by a V 1/2 between −60 and −80 mV.…”

“…As in CP neurons, the threshold of I K activation in these cells is between −45 and −35 mV, i.e., positive to that of I A described in the same cells. Activation (tau ∼10-30 ms at 0 mV) and inactivation (tau more than ∼1 s) of I K are slow, and, in some preparations, inactivation is best described by two exponentials (Beck et al 1992; or is incomplete even during prolonged depolarizing voltage steps (Beck et al 1992;Foehring and Surmeier 1993;Hamill et al 1991;Numann et al 1987). In CP neurons, inactivation of I K is also slow and biexponential (taus = 475 and 3,128 ms) and, in addition, ∼20% of I K is noninactivating.…”

“…Two types of K + currents that are likely to subserve these functions have been described in a number of mammalian CNS neurons: a rapidly activating and inactivating current that is blocked by 4-aminopyridine and usually is referred to as I A (Beck et al 1992;Budde et al 1992;Ficker and Heinemann 1992;Numann et al 1987;Segal and Barker 1984;Storm 1988;Surmeier et al 1989;Wu and Barish 1992); and a 4-aminopyridine-insensitive, delayed, outwardly rectifying K + current, usually referred to as I K (Beck et al 1992;Budde et al 1992;Numann et al 1987;Rudy 1988;Segal and Barker 1984;Storm 1990). These are broad classifications, however, and the detailed time-and voltagedependent properties of the various currents termed I A and I K do vary among cells (Rudy 1988;Storm 1990).…”