Abstract

PEREZ-BONILLA, M. E. et al. Theoretical Study of the Function of the IP3 Receptor/BK Channel Complex in a Single Neuron. Rev. mex. ing. bioméd [online]. 2021, vol.42, n.2, 1125.  Epub June 04, 2021. ISSN 2395-9126.  https://doi.org/10.17488/rmib.42.2.2.

Large conductance calcium-activated potassium (BK) channels carry out many functions in the central nervous system. These channels open in response to increased cytosolic calcium ([Ca2+]cyt) concentration. The influx of calcium ions to the cytosol can occur through voltage-gated calcium channels (VGCCs) on the plasma membrane and/ or through IP3 receptors (IP3-Rs) and ryanodine receptors (RyRs) on the endoplasmic reticulum membrane. The BK channel/IP3-R/RyR interaction has been widely reported in smooth muscle but scarcely investigated in relation to neurons. The aim of this study was to theoretically explore the function of the BK/IP3-R complex by means of a computational model of a neuron that replicates the interaction between the release of Ca2+ from the endoplasmic reticulum (through IP3-Rs) and the opening of the BK channels. The mathematical models are based on the Hodgkin-Huxley formalism and the Goldbeter model. These models were implemented on Visual Basic® and differential equations were solved numerically. Distinct conditions were contemplated for BK conductance and the efflux of endoplasmic Ca2+ to the cytosol. An abrupt rise in [Ca2+]cyt (≥ 5 μM) and short duration (spark) was found to activate BK channels and either pause or stop the action potential train.

Keywords : BK channels; IP3 receptor; Ca²⁺ microdomains; Single-neuron simulations; SERCA pump.