Small-Conductance Ca²⁺-Dependent K⁺ Channels Are the Target of Spike-Induced Ca²⁺ Release in a Feedback Regulation of Pyramidal Cell Excitability

Abstract

Cooperative regulation of inosiol-1,4,5-trisphosphate receptors (IP(3)Rs) by Ca(2+) and IP(3) has been increasingly recognized, although its functional significance is not clear. The present experiments first confirmed that depolarization-induced Ca(2+) influx triggers an outward current in visual cortex pyramidal cells in normal medium, which was mediated by apamin-sensitive, small-conductance Ca(2+)-dependent K(+) channels (SK channels). With IP(3)-mobilizing neurotransmitters bath-applied, a delayed outward current was evoked in addition to the initial outward current and was mediated again by SK channels. Calcium turnover underlying this biphasic SK channel activation was investigated. By voltage-clamp recording, Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCCs) was shown to be responsible for activating the initial SK current, whereas the IP(3)R blocker heparin abolished the delayed component. High-speed Ca(2+) imaging revealed that a biphasic Ca(2+) elevation indeed underlays this dual activation of SK channels. The first Ca(2+) elevation originated from VDCCs, whereas the delayed phase was attributed to calcium release from IP(3)Rs. Such enhanced SK currents, activated dually by incoming and released calcium, were shown to intensify spike-frequency adaptation. We propose that spike-induced calcium release from IP(3)Rs leads to SK channel activation, thereby fine tuning membrane excitability in central neurons.

The Kinetic Profile of Intracellular Calcium Predicts Long-Term Potentiation and Long-Term Depression

“…There is the possibility that at elevated temperatures, different effects on synaptic responses may occur because of effects on certain currents; however, there are at least three reasons for the validity of the analysis at room temperature: (1) strong correlations of differences in the calcium profiles with respect to plasticity outcome (for individual calcium transients and for cumulative calcium rises); (2) distinct differences in the calcium profiles during the control experiments where depolarizing pulses alone are applied and when pairings do not induce plasticity; and (3) a significant difference in the individual calcium transient decay time constants (dendritic and somatic) that occur between the plasticity groups versus the NC groups on the very first pairing. Moreover, previous studies in slices of both basic synaptic physiology-plasticity (Keller et al, 1998;Yoshimura et al, 2000;Gonzalez-Islas and Hablitz, 2003;Hegg et al, 2003;Rae and Irving, 2004;Yamada et al, 2004) and calcium signaling using imaging methods (Miller et al, 1996;PozzoMiller et al, 1999;Kaiser et al, 2004) have been performed at room temperature of 22Ϫ25°C and are consistent with results from other studies at elevated temperatures ranging from 30°C to 37°C in many respects including synaptic properties, plasticity outcomes, and calcium signaling.…”

Competition between Calcium-Activated K+Channels Determines Cholinergic Action on Firing Properties of Basolateral Amygdala Projection Neurons

“…Calcium release from internal stores has been found to activate SK channels in other neurons Williams, 1998, 2000;Morikawa et al, 2003;Yamada et al, 2004;Gulledge and Stuart, 2005;Hagenston et al, 2007). Consistent with this mechanism, the outward current activated by muscarinic agonists in BLA neurons was suppressed by bath application of the SK channel blocker apamin (100 nM), with no effect on the calcium rise.…”

“…However, muscarinic stimulation also generates inositol 1,4,5-trisphosphate (IP 3 ) that releases calcium from intracellular stores, a process that is amplified by AP-evoked calcium influx Sah, 2005, 2007). Store-released calcium activates SK calcium-activated potassium channels in midbrain dopamine neurons Williams, 1998, 2000;Morikawa et al, 2003) and cortical pyramidal neurons (Yamada et al, 2004;Gulledge and Stuart, 2005;Hagenston et al, 2007), consequently modulating neuronal excitability.…”

“…4). In pyramidal neurons in visual cortex, where the AHP is predominantly mediated by the I AHP , IP 3 -CICR results in an enhancement of the AHP and spike-frequency adaptation (Yamada et al, 2004). In BLA projection neurons, the situation is more complex, because the sI AHP is the predominant current responsible for the AHP and spike-frequency adaptation.…”

Functional uncoupling between Ca 2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

“…In the triplet, NMDAR could be replaced by a certain set of cell surface Ca 2ϩ channels. In pyramidal neurons of the visual cortex, inositol 1,4,5-trisphosphate receptors are probably involved in SK channel activation (31), and the triplet could be customized by using inositol 1,4,5-trisphosphate receptors instead of RyRs. Moreover, smooth muscle cells seem to possess a functional communication between RyRs and large-conductance Ca 2ϩ -dependent K ϩ channels (32).…”