- • Active calcium signal propagation occurs when an initial calcium trigger elicits calcium release through endoplasmic reticulum (ER) receptors. A high concentration of the calcium trigger in thin-calibre dendrites would suppress release of calcium through hippocampal inositol trisphosphate receptors (InsP3Rs).
- • Could the high-density expression of A-type K+ channels in thin-calibre dendrites be a mechanism for inhibiting this suppression, thereby restoring the utility of the ER as a substrate for active calcium propagation?
- • Quantitative analyses involving experimentally constrained models reveal a bell-shaped dependence of calcium released through InsP3Rs on the A-type K+ channel density, during the propagation of a calcium wave.
- • A-type K+ channels regulated the relative contribution of ER calcium to the induction of synaptic plasticity in the presence of model metabotropic glutamate receptors.
- • These results identify a novel form of interaction between active dendrites and the ER membrane and suggest that A-type K+ channels are ideally placed for inhibiting the suppression of InsP3Rs in thin-calibre dendrites.
Abstract The A-type potassium current has been implicated in the regulation of several physiological processes. Here, we explore a role for the A-type potassium current in regulating the release of calcium through inositol trisphosphate receptors (InsP3R) that reside on the endoplasmic reticulum (ER) of hippocampal pyramidal neurons. To do this, we constructed morphologically realistic, conductance-based models equipped with kinetic schemes that govern several calcium signalling modules and pathways, and constrained the distributions and properties of constitutive components by experimental measurements from these neurons. Employing these models, we establish a bell-shaped dependence of calcium release through InsP3Rs on the density of A-type potassium channels, during the propagation of an intraneuronal calcium wave initiated through established protocols. Exploring the sensitivities of calcium wave initiation and propagation to several underlying parameters, we found that ER calcium release critically depends on dendritic diameter and that wave initiation occurred at branch points as a consequence of a high surface area to volume ratio of oblique dendrites. Furthermore, analogous to the role of A-type potassium channels in regulating spike latency, we found that an increase in the density of A-type potassium channels led to increases in the latency and the temporal spread of a propagating calcium wave. Next, we incorporated kinetic models for the metabotropic glutamate receptor (mGluR) signalling components and a calcium-controlled plasticity rule into our model and demonstrate that the presence of mGluRs induced a leftward shift in a Bienenstock–Cooper–Munro-like synaptic plasticity profile. Finally, we show that the A-type potassium current could regulate the relative contribution of ER calcium to synaptic plasticity induced either through 900 pulses of various stimulus frequencies or through theta burst stimulation. Our results establish a novel form of interaction between active dendrites and the ER membrane, uncovering a powerful mechanism that could regulate biophysical/biochemical signal integration and steer the spatiotemporal spread of signalling microdomains through changes in dendritic excitability.