P2Y-mediated Ca2+ response is spatiotemporally graded and synchronized in sensory neurons: a two-photon photolysis study.
ATP is thought to be an initiator and modulator of noxious pain sensation. We employed two-photon photolysis to apply ATP locally and transiently, thus mimicking ATP release upon cell damage or exocytosis. Using this technique, an increase in intracellular Ca2+ concentration ([Ca2+]i) was induced via P2Y receptors in individual sensory neurons, or in a neurite region. The ATP-induced [Ca2+]i rise was attenuated by applications of either a phospholipase C inhibitor, or inhibitors for IP3 or ryanodine receptors. These results indicate that intracellular Ca2+ stores play a major role in contributing to the increase in [Ca2+]i. Spatiotemporal analysis revealed that local and transient applications of ATP increased [Ca2+]i by release from intracellular stores, but in a unique, graded, and synchronized manner. 1) As the duration of local ATP application was prolonged, the latency decreased and the magnitude of the [Ca2+]i rise increased; 2) The time course of the rising phase of the [Ca2+]i response to ATP was essentially the same over the cell body, once [Ca2+]i had started to rise. It is anticipated that sensory responses may be modulated variably, depending on the spatiotemporal characteristics of the ATP-related [Ca2+]i profile.
Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shinsuke
S
Nakayama
Toshikazu
T
Yamashita
Masato
M
Konishi
Hiromi
H
Kazama
Shinichiro
S
Kokubun
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010782:Photolysis; D017785:Photons; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013997:Time Factors
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D018048:Receptors, Purinergic P2; D019837:Ryanodine Receptor Calcium Release Channel; D000255:Adenosine Triphosphate; D002118:Calcium