Do canonical transient receptor potential channels mediate cholinergic excitation of cortical pyramidal neurons? 2013

Sameera Dasari, and Joel Abramowitz, and Lutz Birnbaumer, and Allan T Gulledge
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756-0001, USA.

Activation of M1-type muscarinic acetylcholine receptors excites neocortical pyramidal neurons, in part by gating a nonselective cation conductance that produces calcium-dependent 'afterdepolarizing potentials' (ADPs) following short trains of action potentials. Although the identity of the cation conductance mediating the ADP is not known, previous work has implicated canonical transient receptor potential (TRPC) channels, specifically the TRPC5 and TRPC6 subtypes. Using pharmacological and genetic approaches, we tested the role of TRPC channels in generating cholinergic ADPs in layer 5 pyramidal neurons in the mouse medial prefrontal cortex (mPFC). A variety of compounds that block TRPC channels, including 2-aminoethoxydiphenyl borate, flufenamic acid, lanthanum, SKF-96365, and Pyr-3, had little, if any, impact on cholinergic ADPs. Similarly, genetic deletion of several TRPC subunits, including TPRC1, TRPC5, and TRPC6 (single knockouts), or both TRPC5 and TRPC6 together (double knockout), failed to reduce the amplitude of cholinergic ADPs. These data suggest that TRPC5 and TRPC6 subunits are not required for cholinergic excitation of layer 5 pyramidal neurons in the mouse mPFC and that the focus of future work should be expanded to test the involvement of other potential ionic effectors.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010275 Parasympathetic Nervous System The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. Nervous System, Parasympathetic,Nervous Systems, Parasympathetic,Parasympathetic Nervous Systems,System, Parasympathetic Nervous,Systems, Parasympathetic Nervous
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D005071 Evoked Potentials Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported. Event Related Potential,Event-Related Potentials,Evoked Potential,N100 Evoked Potential,P50 Evoked Potential,N1 Wave,N100 Evoked Potentials,N2 Wave,N200 Evoked Potentials,N3 Wave,N300 Evoked Potentials,N4 Wave,N400 Evoked Potentials,P2 Wave,P200 Evoked Potentials,P50 Evoked Potentials,P50 Wave,P600 Evoked Potentials,Potentials, Event-Related,Event Related Potentials,Event-Related Potential,Evoked Potential, N100,Evoked Potential, N200,Evoked Potential, N300,Evoked Potential, N400,Evoked Potential, P200,Evoked Potential, P50,Evoked Potential, P600,Evoked Potentials, N100,Evoked Potentials, N200,Evoked Potentials, N300,Evoked Potentials, N400,Evoked Potentials, P200,Evoked Potentials, P50,Evoked Potentials, P600,N1 Waves,N2 Waves,N200 Evoked Potential,N3 Waves,N300 Evoked Potential,N4 Waves,N400 Evoked Potential,P2 Waves,P200 Evoked Potential,P50 Waves,P600 Evoked Potential,Potential, Event Related,Potential, Event-Related,Potential, Evoked,Potentials, Event Related,Potentials, Evoked,Potentials, N400 Evoked,Related Potential, Event,Related Potentials, Event,Wave, N1,Wave, N2,Wave, N3,Wave, N4,Wave, P2,Wave, P50,Waves, N1,Waves, N2,Waves, N3,Waves, N4,Waves, P2,Waves, P50
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017397 Prefrontal Cortex The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin. Anterior Prefrontal Cortex,Brodmann Area 10,Brodmann Area 11,Brodmann Area 12,Brodmann Area 47,Brodmann's Area 10,Brodmann's Area 11,Brodmann's Area 12,Brodmann's Area 47,Pars Orbitalis,Frontal Sulcus,Gyrus Frontalis Inferior,Gyrus Frontalis Superior,Gyrus Orbitalis,Gyrus Rectus,Inferior Frontal Gyrus,Lateral Orbitofrontal Cortex,Marginal Gyrus,Medial Frontal Gyrus,Olfactory Sulci,Orbital Area,Orbital Cortex,Orbital Gyri,Orbitofrontal Cortex,Orbitofrontal Gyri,Orbitofrontal Gyrus,Orbitofrontal Region,Rectal Gyrus,Rectus Gyrus,Straight Gyrus,Subcallosal Area,Superior Frontal Convolution,Superior Frontal Gyrus,Ventral Medial Prefrontal Cortex,Ventromedial Prefrontal Cortex,Anterior Prefrontal Cortices,Area 10, Brodmann,Area 10, Brodmann's,Area 11, Brodmann,Area 11, Brodmann's,Area 12, Brodmann,Area 12, Brodmann's,Area 47, Brodmann,Area 47, Brodmann's,Area, Orbital,Area, Subcallosal,Brodmanns Area 10,Brodmanns Area 11,Brodmanns Area 12,Brodmanns Area 47,Convolution, Superior Frontal,Convolutions, Superior Frontal,Cortex, Anterior Prefrontal,Cortex, Lateral Orbitofrontal,Cortex, Orbital,Cortex, Orbitofrontal,Cortex, Prefrontal,Cortex, Ventromedial Prefrontal,Cortices, Ventromedial Prefrontal,Frontal Convolution, Superior,Frontal Gyrus, Inferior,Frontal Gyrus, Medial,Frontal Gyrus, Superior,Frontalis Superior, Gyrus,Gyrus, Inferior Frontal,Gyrus, Marginal,Gyrus, Medial Frontal,Gyrus, Orbital,Gyrus, Orbitofrontal,Gyrus, Rectal,Gyrus, Rectus,Gyrus, Straight,Gyrus, Superior Frontal,Inferior, Gyrus Frontalis,Lateral Orbitofrontal Cortices,Olfactory Sulcus,Orbital Areas,Orbital Cortices,Orbital Gyrus,Orbitalis, Pars,Orbitofrontal Cortex, Lateral,Orbitofrontal Cortices,Orbitofrontal Cortices, Lateral,Orbitofrontal Regions,Prefrontal Cortex, Anterior,Prefrontal Cortex, Ventromedial,Prefrontal Cortices, Anterior,Region, Orbitofrontal,Subcallosal Areas,Sulcus, Frontal,Superior Frontal Convolutions,Superior, Gyrus Frontalis,Ventromedial Prefrontal Cortices
D050051 Transient Receptor Potential Channels A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN REPEATS are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES. TRP Cation Channel,Transient Receptor Potential Cation Channel,Transient Receptor Potential Channel,TRP Cation Channels,TRP Membrane Proteins,Transient Receptor Potential Cation Channels,Cation Channel, TRP,Cation Channels, TRP,Channel, TRP Cation,Channels, TRP Cation,Membrane Proteins, TRP,Proteins, TRP Membrane
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D017966 Pyramidal Cells Projection neurons in the CEREBRAL CORTEX and the HIPPOCAMPUS. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. Pyramidal Neurons,Cell, Pyramidal,Cells, Pyramidal,Neuron, Pyramidal,Neurons, Pyramidal,Pyramidal Cell,Pyramidal Neuron
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

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