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The Journal of Neuroscience, January 17, 2007, 27(3):483-495; doi:10.1523/JNEUROSCI.3816-06.2007

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Cellular/Molecular
Nanodomains of Single Ca²⁺ Channels Contribute to Action Potential Repolarization in Cortical Neurons

Andreas Müller,¹ Maria Kukley,¹ Mischa Uebachs,² Heinz Beck,² and Dirk Dietrich¹

Departments of ¹Neurosurgery and ²Epileptology, University Clinic Bonn, 53105 Bonn, Germany

Correspondence should be addressed to Dr. Dirk Dietrich, Department of Neurosurgery, NCH U1 R035, Experimental Neurophysiology, University Clinic Bonn, Sigmund-Freud Street 25, D-53105 Bonn, Germany. Email: dirk.dietrich{at}ukb.uni-bonn.de

The precise shape of action potentials in cortical neurons is a key determinant of action potential-dependent Ca²⁺ influx, as well as of neuronal signaling, on a millisecond scale. In cortical neurons, Ca²⁺-sensitive K⁺ channels, or BK channels (BKChs), are crucial for action potential termination, but the precise functional interplay between Ca²⁺ 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 Ca²⁺ buffers. We find that BKChs are operated by nanodomains of single Ca²⁺ channels. Using a novel approach based on a linear approximation of buffered Ca²⁺ diffusion in microdomains, we quantitatively analyze the prolongation of action potentials by the Ca²⁺ chelator BAPTA. This analysis allowed us to estimate that the mean diffusional distance for Ca²⁺ ions from a Ca²⁺ channel to a BKCh is 13 nm. This surprisingly short diffusional distance cannot be explained by a random distribution of Ca²⁺ channels and renders the activation of BKChs insensitive to the relatively high concentrations of endogenous Ca²⁺ buffers in hippocampal neurons. These data suggest that tight colocalization of the two types of channels permits hippocampal neurons to regulate global Ca²⁺ signals by a high cytoplasmic Ca²⁺ buffer capacity without affecting the fast and brief activation of BKChs required for proper repolarization of action potentials.

Key words: microdomains; calbindin; calcium buffer; action potential; BK channel/Slo; calcium; diffusion; hippocampus; patch clamp

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Received Sept. 1, 2006; revised Nov. 27, 2006; accepted Nov. 27, 2006.

Correspondence should be addressed to Dr. Dirk Dietrich, Department of Neurosurgery, NCH U1 R035, Experimental Neurophysiology, University Clinic Bonn, Sigmund-Freud Street 25, D-53105 Bonn, Germany. Email: dirk.dietrich{at}ukb.uni-bonn.de

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