Presynaptic release probability is increased in hippocampal neurons from ASIC1 knockout mice

被引:52
作者
Cho, Jun-Hyeong [1 ]
Askwith, Candice C. [1 ]
机构
[1] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA
关键词
D O I
10.1152/jn.00940.2007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Acid-sensing ion channels (ASICs) are H+-gated channels that produce transient cation currents in response to extracellular acid. ASICs are expressed in neurons throughout the brain, and ASIC1 knockout mice show behavioral impairments in learning and memory. The role of ASICs in synaptic transmission, however, is not thoroughly understood. We analyzed the involvement of ASICs in synaptic transmission using microisland cultures of hippocampal neurons from wild-type and ASIC knockout mice. There was no significant difference in single action potential (AP)-evoked excitatory postsynaptic currents (EPSCs) between wild-type and ASIC knockout neurons. However, paired-pulse ratios (PPRs) were reduced and spontaneous miniature EPSCs (mEPSCs) occurred at a higher frequency in ASIC1 knockout neurons compared with wildtype neurons. The progressive block of NMDA receptors by an open channel blocker, MK-801, was also faster in ASIC1 knockout neurons. The amplitude and decay time constant of mEPSCs, as well as the size and refilling of the readily releasable pool, were similar in ASIC1 knockout and wild-type neurons. Finally, the release probability, which was estimated directly as the ratio of AP-evoked to hypertonic sucrose-induced charge transfer, was increased in ASIC1 knockout neurons. Transfection of ASIC1a into ASIC1 knockout neurons increased the PPRs, suggesting that alterations in release probability were not the result of developmental compensation within the ASIC1 knockout mice. Together, these findings demonstrate that neurons from ASIC1 knockout mice have an increased probability of neurotransmitter release and indicate that ASIC1a can affect presynaptic mechanisms of synaptic transmission.
引用
收藏
页码:426 / 441
页数:16
相关论文
共 61 条
[1]   Distinct structural and ionotropic roles of NMDA receptors in controlling spine and synapse stability [J].
Alvarez, Veronica A. ;
Ridenour, Dennis A. ;
Sabatini, Bernardo L. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (28) :7365-7376
[2]   Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons [J].
Askwith, CC ;
Wemmie, JA ;
Price, MP ;
Rokhlina, T ;
Welsh, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (18) :18296-18305
[3]   The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties [J].
Bassilana, F ;
Champigny, G ;
Waldmann, R ;
deWeille, JR ;
Heurteaux, C ;
Lazdunski, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (46) :28819-28822
[4]   Temporal synaptic tagging by Ih activation and actin:: Involvement in long-term facilitation and cAMP-induced synaptic enhancement [J].
Beaumont, V ;
Zhong, N ;
Froemke, RC ;
Ball, RW ;
Zucker, RS .
NEURON, 2002, 33 (04) :601-613
[5]   Enhancement of synaptic transmission by cyclic AMP modulation of presynaptic Ih channels [J].
Beaumont, V ;
Zucker, RS .
NATURE NEUROSCIENCE, 2000, 3 (02) :133-141
[6]   EXCITATORY AND INHIBITORY AUTAPTIC CURRENTS IN ISOLATED HIPPOCAMPAL-NEURONS MAINTAINED IN CELL-CULTURE [J].
BEKKERS, JM ;
STEVENS, CF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) :7834-7838
[7]   Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons [J].
Benson, CJ ;
Xie, JH ;
Wemmie, JA ;
Price, MP ;
Henss, JM ;
Welsh, MJ ;
Snyder, PM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) :2338-2343
[8]   Acid-sensing ion channels in malignant gliomas [J].
Berdiev, BK ;
Xia, JZ ;
McLean, LA ;
Markert, JM ;
Gillespie, GY ;
Mapstone, TB ;
Naren, AP ;
Jovov, B ;
Bubien, JK ;
Ji, HL ;
Fuller, CM ;
Kirk, KL ;
Benos, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (17) :15023-15034
[9]   Short-term synaptic plasticity: A comparison of two synapses [J].
Blitz, DM ;
Foster, KA ;
Regehr, WG .
NATURE REVIEWS NEUROSCIENCE, 2004, 5 (08) :630-640
[10]   Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse [J].
Chavis, P ;
Westbrook, G .
NATURE, 2001, 411 (6835) :317-321