Distinct Ca 2+ Sources in Dendritic Spines of Hippocampal CA1 Neurons Couple to SK and K v 4 Channels

Abstract

SUMMARY Ca2+-activated SK channels and voltage-gated A-type Kv4 channels shape dendritic excitatory postsynaptic potentials (EPSPs) in hippocampal CA1 pyramidal neurons. Synaptically evoked Ca2+ influx through N-methyl-D-aspartate receptors (NMDARs) activates spine SK channels, reducing EPSPs and the associated spine head Ca2+ transient. However, results using glutamate uncaging implicated Ca2+ influx through SNX-482 (SNX) sensitive Cav2.3 (R-type) Ca2+ channels as the Ca2+ source for SK channel activation. The present findings show that using Schaffer collateral stimulation the effects of SNX and apamin are not mutually exclusive and SNX increases EPSPs independent of SK channel activity. Dialysis with 1,2-bis(o-aminophenoxy)ethane-N’N’N’-tetraacetic acid (BAPTA), application of 4-Aminopyridine (4-AP), expression of a Kv4.2 dominant negative subunit, and dialysis with a KChIPs antibody occluded the SNX-induced increase of EPSPs. The results suggest two distinct Ca2+ signaling pathways within dendritic spines, that links Ca2+ influx through NMDARs to SK channels and Ca2+ influx through R-type Ca2+ channels to Kv4.2-containing channels.

Location matters: somatic and dendritic SK channels answer to distinct calcium signals

“…Consistent with this observation, specific coupling of SK channels to dendritic R-type calcium channels has been demonstrated elsewhere (Bloodgood and Sabatini 2007), suggesting that this coupling scheme may be used in many types of neurons, although other calcium sources for SK channels have been described as well (Marrion and Tavalin 1998; Ngo-Anh et al. 2005;Wang et al 2014;Wolfart and Roeper 2002). The dominant role of R-type channels in activating SK channels in dendrites may be advantageous for two reasons.…”

“…The close association of depolarization-dependent calcium influx through VDCCs and activation of hyperpolarizing potassium conductances allows K Ca channels to control excitability, action potential waveform, and spike patterns in many types of neurons (Faber 2010; Swensen and Bean 2003;Wolfart and Roeper 2002;Womack and Khodakhah 2003). Recent evidence also suggests that K Ca channels locally attenuate excitability and regulate synaptic integration in dendritic spines of hippocampal pyramidal neurons during calcium influx through glutamate receptors and VDCCs (Bloodgood and Sabatini 2007;Cai et al 2004; Ngo-Anh et al 2005;Wang et al 2014). These findings suggest that K Ca channels are expressed in various neuronal compartments; however, the conditions under which they are activated, the coupling specificity to their calcium source, and their intraneuronal distribution remain incompletely understood.…”

“…Immunohistochemistry, or for better spatial resolution, array tomography and electron microscopy combined with immunogold labeling, could be used to examine the distribution of SK channels. In the future, photocaged and fluorescently labeled inhibitors of SK channels and VDCCs may allow for spatially restricted inhibition of these ion channels and the detection of their distribution, respectively, but such elegant strategies are still limited to a small number of ion channel subtypes (Schmidt et al 2014;Williams et al 2012;Zayat et al 2003).In the next set of experiments, the authors seek to determine the calcium source activating dendritic SK channels. They find that inhibition of R-type calcium channels occludes the effect of apamin, suggesting that they directly couple to the calciumbinding domains of SK channels (Fig.…”

“…5, Jones and Stuart). Additionally, altered buffering of calcium can disrupt many more processes, including neurotransmitter release (Bucurenciu et al 2008), synaptic plasticity (Caillard et al 2000; Matveev et al 2006), and gene transcription (West et al 2001). New GECIs with fewer calcium binding sites (Thestrup et al 2014) may allow for less alteration of intracellular calcium dynamics, and therefore preserved coupling of calcium to its effectors.…”

β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus

“…2). For example, Kim et al 2007;Kim and Hoffman 2008;Lin et al 2008;Wang et al 2014). In addition, the back-propagation of somatically generated action potentials into pyramidal cell dendrites is another potentially important source of postsynaptic depolarization needed for NMDAR activation and LTP induction (Watanabe et al 2002) and dendritically localized Kv4.2/A-type potassium channels can strongly attenuate action potential back-propagation (Hoffman et al 1997;Chen et al 2006).…”