A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons

Abstract

1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX-resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons.

Hippocampal long-lasting potentiation produced by pairing single volleys and brief conditioning tetani evoked in separate afferents

“…Even in the presence of picrotoxin and related GABA antagonists, there remains a later, more slowly developing, synaptic inhibition (Newberry and Nicoll, 1984), which will curtail the synaptic depolarization during the longer trains and thereby cause fewer conditioning effects. Moreover, the synaptically evoked firing of the cells will lead to spike-evoked afterhyperpolarizations (Hotson and Prince, 1980), which will further decrease the synaptic depolarization.…”

Regional Differences in Distribution and Functional Expression of Small-Conductance Ca2+-Activated K+Channels in Rat Brain

“…5A). The early outward tail current contributes to the mAHP (Storm, 1989;Stocker et al, 1999), whereas the slow component, lasting 4 -7 sec, is called the I sAHP because it underlies the slow AHP (Hotson and Prince, 1980;Lancaster and Adams, 1986;Storm, 1990;Sah, 1996). Both I sAHP and the apamin-sensitive component of the mAHP current were largely resistant to 5 mM TEA but were readily suppressed by perfusion with Ca 2ϩ -free medium and by the Ca 2ϩ channel blockers Mn 2ϩ and Cd 2ϩ (data not shown; Lancaster and Adams, 1986;Pedarzani and Storm, 1993;Stocker et al, 1999).…”

Mechanisms of physiological and epileptic HFO generation

“…In general these oscillations depend on a voltage-gated inward current, of Na + and Ca 2+ ions, and outward currents of one or more of the many kinds of K + channels. Perhaps the most straightforward conceptually is an oscillation where Ca 2+ influx activates a Ca 2+ -dependent K + conductance that mediates a relatively slow afterhyperpolarization (Hotson and Prince, 1980;Jahnsen and Llinas, 1984;Kandel and Spencer, 1961;Leresche et al, 1991;Llinas, 1988;Traub et al, 1993;Wong and Prince, 1978). Dendritic P/Q type calcium channels can generate intrinsic oscillations in vitro of relatively high frequencies (20-80 Hz) (Pedroarena and Llinas, 1997).…”