Hippocalcin gates the calcium activation of the slow afterhyperpolarization in hippocampal pyramidal cells.
In the brain, calcium influx following a train of action potentials activates potassium channels that mediate a slow afterhyperpolarization current (I(sAHP)). The key steps between calcium influx and potassium channel activation remain unknown. Here we report that the key intermediate between calcium and the sAHP channels is the diffusible calcium sensor hippocalcin. Brief depolarizations sufficient to activate the I(sAHP) in wild-type mice do not elicit the I(sAHP) in hippocalcin knockout mice. Introduction of hippocalcin in cultured hippocampal neurons leads to a pronounced I(sAHP), while neurons expressing a hippocalcin mutant lacking N-terminal myristoylation exhibit a small I(sAHP) that is similar to that recorded in uninfected neurons. This implies that hippocalcin must bind to the plasma membrane to mediate its effects. These findings support a model in which the calcium sensor for the sAHP channels is not preassociated with the channel complex.
Tzingounis
Anastassios V
AV
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
Kobayashi
Masaaki
M
Takamatsu
Ken
K
Nicoll
Roger A
RA
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051597:Hippocalcin / Q000172:deficiency / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D014162:Transfection / Q000379:methods
D018797:Cell Cycle Proteins; C115270:G2A receptor; D026902:Potassium Channel Blockers; D043562:Receptors, G-Protein-Coupled; D051640:Small-Conductance Calcium-Activated Potassium Channels; D049452:Green Fluorescent Proteins; D051597:Hippocalcin; D004533:Egtazic Acid; D002118:Calcium