Nanodomains of Single Ca 2+ Channels Contribute to Action Potential Repolarization in Cortical Neurons

• Published in: The Journal of neuroscience Vol. 27; no. 3; pp. 483 - 495
• Main Authors: Müller, Andreas, Kukley, Maria, Uebachs, Mischa, Beck, Heinz, Dietrich, Dirk
• Format: Journal Article
• Language: English
• Published: 17.01.2007
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.3816-06.2007

The precise shape of action potentials in cortical neurons is a key determinant of action potential-dependent Ca 2+ influx, as well as of neuronal signaling, on a millisecond scale. In cortical neurons, Ca 2+ -sensitive K + channels, or BK channels (BKChs), are crucial for action potential termination, but the precise functional interplay between Ca 2+ channels and BKChs has remained unclear. In this study, we investigate the mechanisms allowing for rapid and reliable activation of BKChs by single action potentials in hippocampal granule cells and the impact of endogenous Ca 2+ buffers. We find that BKChs are operated by nanodomains of single Ca 2+ channels. Using a novel approach based on a linear approximation of buffered Ca 2+ diffusion in microdomains, we quantitatively analyze the prolongation of action potentials by the Ca 2+ chelator BAPTA. This analysis allowed us to estimate that the mean diffusional distance for Ca 2+ ions from a Ca 2+ channel to a BKCh is ∼13 nm. This surprisingly short diffusional distance cannot be explained by a random distribution of Ca 2+ channels and renders the activation of BKChs insensitive to the relatively high concentrations of endogenous Ca 2+ buffers in hippocampal neurons. These data suggest that tight colocalization of the two types of channels permits hippocampal neurons to regulate global Ca 2+ signals by a high cytoplasmic Ca 2+ buffer capacity without affecting the fast and brief activation of BKChs required for proper repolarization of action potentials.