Storozhuk Maksim V, Ivanova Svetlana Y, Balaban Pavel M, Kostyuk Platon G
A.A. Bogomoletz Institute of Physiology, Kiev, Ukraine.
Synapse. 2005 Oct;58(1):45-52. doi: 10.1002/syn.20186.
It has been previously demonstrated that mitochondria are of crucial importance for posttetanic potentiation (PTP) at neuromuscular junction. The aim of our study was to examine whether this may also be the case at a central synapse. To address this question, we studied possible mitochondrial involvement in PTP of GABAergic synaptic transmission in rat neocortical cultures, a preparation in which PTP has not been previously documented. Synaptic responses were evoked by local extracellular stimulation. Whole-cell patch-clamp technique was employed to record inhibitory postsynaptic currents (IPSCs) from postsynaptic neurons. Tetanic stimulation (30 Hz, 4 s) of the presynaptic neuron evoked an increase of IPSC amplitude, lasting for about 1 min. PTP was accompanied by a decrease of coefficient of variation of the IPSC and a decrease of paired-pulse (IPSC(2)/IPSC(1)) ratio, indicating involvement of presynaptic mechanism(s) in PTP. Possible role of mitochondria in PTP was addressed using drugs affecting Ca(2+) uptake and subsequent Ca(2+) efflux: carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and tetraphenylphosphonium ions (TPP(+)). It was found that both CCCP (1-2 microM) and TPP(+) (10 microM) either substantially decreased or eliminated PTP. These results further confirm presynaptic origin of PTP in neocortical neurons and suggest an important role of mitochondrial Ca(2+) turnover in this form of synaptic plasticity at the central synapse.
先前已经证明，线粒体对于神经肌肉接头处的强直后增强（PTP）至关重要。我们研究的目的是检验在中枢突触处是否也是这种情况。为了解决这个问题，我们研究了大鼠新皮质培养物中GABA能突触传递的PTP中线粒体可能的参与情况，此前尚未有关于该培养物中PTP的记录。通过局部细胞外刺激诱发突触反应。采用全细胞膜片钳技术记录突触后神经元的抑制性突触后电流（IPSCs）。对突触前神经元进行强直刺激（30Hz，4s）可诱发IPSC幅度增加，持续约1分钟。PTP伴随着IPSC变异系数的降低和双脉冲（IPSC(2)/IPSC(1)）比率的降低，表明突触前机制参与了PTP。使用影响Ca(2+)摄取及随后Ca(2+)外流的药物：羰基氰3-氯苯腙（CCCP）和四苯基鏻离子（TPP(+)）来研究线粒体在PTP中的可能作用。发现CCCP（1-2 microM）和TPP(+)（10 microM）均显著降低或消除了PTP。这些结果进一步证实了新皮质神经元中PTP的突触前起源，并表明线粒体Ca(2+)周转在中枢突触这种形式的突触可塑性中起重要作用。
