2007 Fiscal Year Final Research Report Summary
Study on the mechanisms underlying the depolarization induced intracellular calcium release in CNS neurons
| Project/Area Number |
18500311
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | National Institute for Physiological Sciences |
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Principal Investigator |
ISHIBASHI Hitoshi National Institute for Physiological Sciences, Department of Developmental Physiology, Associate Professor (50311874)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Calcium store / Depolarization / High-potassium stimulation / Central nervous system / Glycine release / Phospholipase C / Neuron |
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| Research Abstract |
It is well established that entry of Ca^<2+> through voltage-dependent Ca^<2+> channels plays a crucial role in the depolarization-induced release of neurotransmitters from presynaptic nerve terminals. In addition to this depolarization-induced Ca^<2+>-influx, several studies have suggested that presynaptic depolarization per se can control the exocytotic machinery and promote neurotransmitter release even in the absence of extracellular Ca^<2+>. In the present study, the high potassium-induced potentiation of spontaneous glycine and GABA release in extracellular Ca^<2+>-free conditions was studied in mechanically dissociated rat spinal dorsal horn and hippocampal neurons using whole-cell patch-clamp technique, respectively. The high K^+-induced elevation of intracellular Ca^<2+> concentration in the isolated neurons was also studied. Elevating extracellular K^+ concentration reversibly increased the frequency of spontaneous glycinergic and GABAergic inhibitory postsynaptic currents (IPSCs) in the absence of extracellular Ca2+. Blocking voltage-dependent Na+ channels (tetrodotoxin) and Ca^<2+> channels (nifedipine and omega-grammotoxin-SIA) had no effect on this potassium-induced potentiation of transmitter release. The high potassium-induced increase in IPSC frequency was also observed in the absence of extracellular Na^+, although the recovery back to baseline levels of release was prolonged under these conditions. The action of high potassium solution on glycine release was prevented by BAPTA-AM, by depletion of intracellular Ca^<2+> stores by thapsigargin and by the phospholipase C inhibitor U-73122. The results suggest that the elevated extracellular K^+ concentration causes Ca2+ release from internal stores which is independent of extracellular Na^+-and Ca^<2+>-influx, and may reveal a novel mechanism by which the potassium-induced depolarization of presynaptic nerve terminals can regulate intracellular Ca^<2+> concentration and exocytosis.
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Research Products
(28 results)
