Properties of a Calcium-Activated K+ Current on Interneurons in the Developing Rat Hippocampus

Abstract

Calcium-activated potassium currents have an essential role in regulating excitability in a variety of neurons. Although it is well established that mature CA1 pyramidal neurons possess a Ca2+-activated K+ conductance ( I K(Ca)) with early and late components, modulation by various endogenous neurotransmitters, and sensitivity to K+ channel toxins, the properties of I K(Ca) on hippocampal interneurons (or immature CA1 pyramidal neurons) are relatively unknown. To address this problem, whole-cell voltage-clamp recordings were made from visually identified interneurons in stratum lacunosum-moleculare (L-M) and CA1 pyramidal cells in hippocampal slices from immature rats (P3–P25). A biphasic calcium-activated K+ tail current was elicited following a brief depolarization from the holding potential (−50 mV). Analysis of the kinetic properties of I K(Ca)suggests that an early current component differs between these two cell types. An early I K(Ca) with a large peak current amplitude (200.8 ± 13.2 pA, mean ± SE), slow time constant of decay (70.9 ± 3.3 ms), and relatively rapid time to peak (within 15 ms) was observed on L-M interneurons ( n = 88), whereas an early I K(Ca) with a small peak current amplitude (112.5 ± 7.3 pA), a fast time constant of decay (39.4 ± 1.6 ms), and a slower time-to-peak (within 26 ms) was observed on CA1 pyramidal neurons ( n = 85). Removal of extracellular calcium or addition of inorganic Ca2+ channel blockers (cadmium, nickel, or cobalt) was used to demonstrate the calcium dependence of these currents. Addition of norepinephrine, carbachol, and a variety of channel toxins (apamin, iberiotoxin, verruculogen, paxilline, penitrem A, and charybdotoxin) were used to further distinguish between I K(Ca) on these two hippocampal cell types. Verruculogen (100 nM), carbachol (100 μM), apamin (100 nM), TEA (1 mM), and iberiotoxin (50 nM) significantly reduced early I K(Ca) on CA1 pyramidal neurons; early I K(Ca) on L-M interneurons was inhibited by apamin and TEA. Combined with previous work showing that the firing properties of hippocampal interneurons and pyramidal cells differ, our kinetic and pharmacological data provide strong support for the hypothesis that different types of Ca2+-activated K+ current are present on these two cell types.