Reduced IP3 sensitivity of IP3 receptor in Purkinje neurons

The inositol 1,4,5-trisphosphate receptor (IP3R) is highly expressed in Purkinje neurons (PNs) and is thought to be essential for the induction of long-term depression at parallel-fiber–PN synapses. Here, by imaging the fluorescence intensity of the low-affinity Ca2+ indicator inside the Ca2+ stores in the permeabilized single PNs, we analyzed the kinetics of Ca2+ release via the IP3R in controlled cytoplasmic environments. The rate of Ca2+ release is dependent on the IP3 concentration with an EC50 of 25.8 μM, which is > 20-fold greater than that of the IP3R in the isolated preparations or in peripheral cells. This property would be advantageous in inducing the release of Ca2+ in a localized space adjacent to the site of synaptic inputs.

[1]  M. Iino,et al.  Ca2+‐sensor region of IP3 receptor controls intracellular Ca2+ signaling , 2001 .

[2]  M. Kano,et al.  Local Calcium Release in Dendritic Spines Required for Long-Term Synaptic Depression , 2000, Neuron.

[3]  I. Moraru,et al.  An endogenous sulfated inhibitor of neuronal inositol trisphosphate receptors. , 2000, Biochemistry.

[4]  M. Womack,et al.  Impaired Calcium Release in Cerebellar Purkinje Neurons Maintained in Culture , 2000, The Journal of general physiology.

[5]  A. Weidema,et al.  The Bell-shaped Ca2+ Dependence of the Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Is Modulated by Ca2+/Calmodulin* , 1999, The Journal of Biological Chemistry.

[6]  S. Snyder,et al.  Differential cellular expression of isoforms of inositol 1,4,5‐triphosphate receptors in neurons and glia in brain , 1999, The Journal of comparative neurology.

[7]  George J. Augustine,et al.  Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites , 1998, Nature.

[8]  M. Berridge Neuronal Calcium Signaling , 1998, Neuron.

[9]  I. Bezprozvanny,et al.  Functional Coupling of Phosphatidylinositol 4,5-Bisphosphate to Inositol 1,4,5-Trisphosphate Receptor* , 1998, The Journal of Biological Chemistry.

[10]  M. Iino,et al.  Allosteric regulation by cytoplasmic Ca2+ and IP3 of the gating of IP3 receptors in permeabilized guinea‐pig vascular smooth muscle cells , 1998, The Journal of physiology.

[11]  G. Hajnóczky,et al.  Minimal requirements for calcium oscillations driven by the IP3 receptor , 1997, The EMBO journal.

[12]  K. Mikoshiba,et al.  Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor , 1996, Nature.

[13]  Richard F. Thompson,et al.  Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKCγ mutant mice , 1995, Cell.

[14]  K. Khodakhah,et al.  Fast activation and inactivation of inositol trisphosphate‐evoked Ca2+ release in rat cerebellar Purkinje neurones. , 1995, The Journal of physiology.

[15]  R. Wojcikiewicz,et al.  Type I, II, and III inositol 1,4,5-trisphosphate receptors are unequally susceptible to down-regulation and are expressed in markedly different proportions in different cell types , 1995, The Journal of Biological Chemistry.

[16]  H. Kasai,et al.  Spatial dynamics of second messengers: IP3 and cAMP as long-range and associative messengers , 1994, Trends in Neurosciences.

[17]  K. Hirose,et al.  Heterogeneity of channel density in inositol-1,4,5-trisphosphate-sensitive Ca2+ stores , 1994, Nature.

[18]  S. Tonegawa,et al.  Reduced hippocampal long-term potentiation and context-specific deficit in associative learning in mGluR1 mutant mice , 1994, Cell.

[19]  S. Tonegawa,et al.  Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice , 1994, Cell.

[20]  K. Khodakhah,et al.  Functional heterogeneity of calcium release by inositol trisphosphate in single Purkinje neurones, cultured cerebellar astrocytes, and peripheral tissues. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[21]  T. Machen,et al.  Technique for in situ measurement of calcium in intracellular inositol 1,4,5-trisphosphate-sensitive stores using the fluorescent indicator mag-fura-2. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[22]  A. Konnerth,et al.  Brief dendritic calcium signals initiate long-lasting synaptic depression in cerebellar Purkinje cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Iino,et al.  Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca release in smooth muscle cells of the guinea pig taenia caeci , 1990, The Journal of general physiology.

[24]  M. Sakurai Calcium is an intracellular mediator of the climbing fiber in induction of cerebellar long-term depression. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[25]  W. N. Ross,et al.  Mapping calcium transients in the dendrites of Purkinje cells from the guinea‐pig cerebellum in vitro. , 1987, The Journal of physiology.

[26]  M. Ito,et al.  Long-term depression. , 1989, Annual review of neuroscience.