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M‐type potassium channels modulate Schaffer collateral–CA1 glutamatergic synaptic transmission
Author(s) -
Sun Jianli,
Kapur Jaideep
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.235820
Subject(s) - glutamatergic , neurotransmission , neuroscience , excitatory postsynaptic potential , schaffer collateral , chemistry , glutamate receptor , biology , receptor , inhibitory postsynaptic potential , biochemistry
Key points• M‐type potassium channels play a key role in modulating neuronal excitability. However, the effects of M‐channel activation on synaptic transmission are poorly understood. • This study found that an M1 receptor agonist and M‐channel blockers increased action potential‐independent glutamate release at Schaffer collateral–CA1 pyramidal neuron synapses in acute hippocampus slices. • This enhancement was dependent on Ca 2+ influx from extracellular space but not intracellular calcium stores. • Inhibition of M‐channels results in the depolarization of CA3 pyramidal neurons and activated presynaptic voltage‐gated P/Q‐ and N‐type calcium channels, which in turn causes Ca 2+ influx and increased glutamate release. • Thus, M1 muscarinic agonists modulate action potential‐independent glutamatergic synaptic transmission in the hippocampus by inhibition of presynaptic M‐channels.Abstract Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M‐type potassium channels mediate the effects of muscarinic activation in the hippocampus, and it has been proposed that they modulate glutamatergic synaptic transmission. We tested whether M1 muscarinic receptor activation enhances glutamatergic synaptic transmission via the inhibition of the M‐type potassium channels that are present in Schaffer collateral axons and terminals. Miniature excitatory postsynaptic currents (mEPSCs) were recorded from CA1 pyramidal neurons. The M1 receptor agonist, NcN‐A‐343, increased the frequency of mEPSCs, but did not alter their amplitude. The M‐channel blocker XE991 and its analogue linopirdine also increased the frequency of mEPSCs. Flupirtine, which opens M‐channels, had the opposite effect. XE991 did not enhance mEPSCs frequency in a calcium‐free external medium. Blocking P/Q‐ and N‐type calcium channels abolished the effect of XE991 on mEPSCs. These data suggested that the inhibition of M‐channels increases presynaptic calcium‐dependent glutamate release in CA1 pyramidal neurons. The effects of these agents on the membrane potentials of presynaptic CA3 pyramidal neurons were studied using current clamp recordings; activation of M1 receptors and blocking M‐channels depolarized neurons and increased burst firing. The input resistance of CA3 neurons was increased by the application of McN‐A‐343 and XE991; these effects were consistent with the closure of M‐channels. Muscarinic activation inhibits M‐channels in CA3 pyramidal neurons and its efferents – Schaffer collateral, which causes the depolarization, activates voltage‐gated calcium channels, and ultimately elevates the intracellular calcium concentration to increase the release of glutamate on CA1 pyramidal neurons.