Muscarinic activation of inwardly rectifying K+ conductance reduces EPSPs in rat hippocampal CA1 pyramidal cells
Article first published online: 5 AUG 2004
The Journal of Physiology
Volume 535, Issue 2, pages 383–396, September 2001
How to Cite
Seeger, T. and Alzheimer, C. (2001), Muscarinic activation of inwardly rectifying K+ conductance reduces EPSPs in rat hippocampal CA1 pyramidal cells. The Journal of Physiology, 535: 383–396. doi: 10.1111/j.1469-7793.2001.00383.x
- Issue published online: 5 AUG 2004
- Article first published online: 5 AUG 2004
- (Resubmitted 13 March 2001; accepted after revision 2 May 2001)
- 1To determine how acetylcholine (ACh) modulates the somatodendritic processing of EPSPs, we performed whole-cell recordings from CA1 pyramidal cells of hippocampal slices and examined the effect of the cholinergic agonist, carbachol (CCh), on α-amino-3-hydroxy-5-methyl isoxazole-4-propionate (AMPA) EPSPs, miniature EPSPs, and EPSP-like waveforms evoked by brief dendritic glutamate pulses (glutamate-evoked postsynaptic potentials, GPSPs).
- 2Although CCh is known to enhance the intrinsic excitability of the neuron in several ways, activation of atropine-sensitive (muscarinic) receptors on the apical dendrite or the soma of CA1 pyramidal cells consistently reduced the amplitude of EPSPs and GPSPs.
- 3Cholinergic inhibition of evoked and simulated EPSP waveforms displayed considerable voltage dependence, with the amplitude of the postsynaptic potentials progressively declining with membrane hyperpolarization indicating the involvement of an inwardly rectifying current.
- 4Extracellular Ba2+ (200 μm) and tertiapin (30 nm), a novel and selective blocker of G protein-activated, inwardly rectifying K+ (GIRK) channels, completely blocked the effect of CCh on GPSP amplitude.
- 5Muscarinic reduction of GPSPs was not sensitive to the M1 receptor-preferring antagonist, pirenzepine, but was suppressed by the M2 receptor-preferring antagonist, methoctramine, and by the allosteric M2 receptor antagonist, gallamine.
- 6In voltage-clamp recordings, CCh induced an ion current displaying inward rectification in the hyperpolarizing direction, which was identified as a GIRK current based on its sensitivity to low Ba2+ and tertiapin. Its pharmacological profile paralleled that of the cholinergic GPSP reduction.
- 7We link the observed reduction of postsynaptic potentials to the cholinergic activation of a GIRK conductance, which serves to partially shunt excitatory synaptic input.