Ca2+ signaling in mouse cortical neurons studied by two-photon imaging and photoreleased inositol triphosphate.
IP(3)-mediated Ca(2+) release is a crucial neuronal signaling mechanism that has not been extensively characterized in the mammalian cerebral cortex. We used two-photon, video-rate microscopy to image Ca(2+) signals evoked by photoreleased IP(3) in pyramidal neurons of mouse prefrontal cortex. Ca(2+) responses to photoreleased IP(3) varied greatly between different neurons; however, within IP(3)-responsive neurons, the soma invariably showed highest sensitivity, with signals increasing nonlinearly with [IP(3)]. Responses to paired photorelease displayed inhibition, whereas IP(3)-evoked Ca(2+) liberation was potentiated by Ca(2+) entry during action potentials and vice versa. IP(3)-mediated Ca(2+) signals strongly inhibited spike firing through activation of K(+) membrane conductance. Metabotropic signaling via the phosphoinositide pathway thus serves as a powerful and sustained modulator of excitability in cortical neurons and displays complex reciprocal interactions between electrical and chemical signals.
Stutzmann
Grace E
GE
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697-4550, USA. grace@uci.edu
LaFerla
Frank M
FM
Parker
Ian
I
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002462:Cell Membrane / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology / Q000528:radiation effects; D007834:Lasers; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010782:Photolysis; D017785:Photons; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D014466:Ultraviolet Rays
D005456:Fluorescent Dyes; C061868:inositol 1,4,5-trisphosphate 1-(2-nitrophenyl)ethyl ester; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium