Protein kinase C as mediator of arachidonic acid-induced decrease of neuronal M current

Schmitt, Hans‐Georg; Meves, H.

doi:10.1007/bf00374513

Cited by 22 publications

(13 citation statements)

References 18 publications

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“…In frog sympathetic neurones, smooth muscle cells and NG108‐15 neuroblastoma–glioma cells, phorbol esters or diacylglycerols suppress the M‐current (Higashida & Brown, 1986; Brown & Higashida, 1988; Pfaffinger et al 1988). In NG108‐15 cells, moreover, PKC 19–31 peptide, an effective inhibitor of PKC, elicits a shift in the voltage dependence of the M‐current such that the V ½ goes from −34 mV to −44 mV (Schmitt & Meves, 1993). However, because the inhibition induced by phorbol esters or diacylglycerols is partial at most, and because PKC inhibitors fail to prevent receptor‐mediated M‐current inhibition, PKC has not been considered necessary for muscarinic inhibition (Bosma & Hille, 1989; Chen et al 1994).…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C shifts the voltage dependence of KCNQ/M channels expressed in Xenopus oocytes

Nakajo

Kubo

2005

The Journal of Physiology

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It is well established that stimulation of G q -coupled receptors such as the M1 muscarinic acetylcholine receptor inhibits KCNQ/M currents. While it is generally accepted that this muscarinic inhibition is mainly caused by the breakdown of PIP 2 , the role of the subsequent activation of protein kinase C (PKC) is not well understood. By reconstituting M currents in Xenopus oocytes, we observed that stimulation of coexpressed M1 receptors with 10 µM oxotremorine M (oxo-M) induces a positive shift (4-30 mV, depending on which KCNQ channels are expressed) in the conductance-voltage relationship (G-V ) of KCNQ channels. When we applied phorbol 12-myristate 13-acetate (PMA), a potent PKC activator, we observed a large positive shift (17.8 ± 1.6 mV) in the G-V curve for KCNQ2, while chelerythrine, a PKC inhibitor, attenuated the shift caused by the stimulation of M1 receptors. By contrast, reducing PIP 2 had little effect on the G-V curve for KCNQ2 channels; although pretreating cells with 10 µM wortmannin for 30 min reduced KCNQ2 current amplitude by 80%, the G-V curve was shifted only slightly (5 mV). Apparently, the shift induced by muscarinic stimulation in Xenopus oocytes was mainly caused by PKC activation. When KCNQ2/3 channels were expressed in HEK 293T cells, the G-V curve seemed already to be shifted in a positive direction, even before activation of PKC, and PMA failed to shift the curve any further. That alkaline phosphatase in the patch pipette shifted the G-V curve in a negative direction suggests KCNQ2/3 channels are constitutively phosphorylated in HEK 293T cells.

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Section: Discussionmentioning

confidence: 99%

Protein kinase C shifts the voltage dependence of KCNQ/M channels expressed in Xenopus oocytes

Nakajo

Kubo

2005

The Journal of Physiology

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“…M 1 receptors are classically linked via G q and phospholipase C activation to the generation of two important signaling molecules: IP 3 (the endogenous ligand for IP 3 receptors) and diacylglycerol (DAG). DAG is an activator of protein kinase C, which can downregulate the M current (Schmitt and Meves, 1993). DAG can also directly activate some nonspecific cation conductances (Hofmann et al, 1999).…”

Section: Pharmacology Of Cholinergic Signalingmentioning

confidence: 99%

Cholinergic Inhibition of Neocortical Pyramidal Neurons

Gulledge¹,

Stuart²

2005

J. Neurosci.

173

128

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“…The biphasic effect of AA on IM, of an initial increase followed by a decrease, was also observed by others (Behe, Sandmeier & Meves, 1992). The underlying mechanism is obscure, though PKC was indicated as mediating the suppressing effect of AA on IM (Schmitt & Meves, 1993); and AA, indeed, may activate…”

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confidence: 99%

Roles of arachidonic acid, lipoxygenases and phosphatases in calcium‐dependent modulation of M‐current in bullfrog sympathetic neurons.

1995

The Journal of Physiology

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1. M-current (IM) is regulated by intracellular free Ca2P ([Ca2+]1). Suppression and overrecovery of IM induced by muscarine and luteinizing-hormone releasing hormone (LHRH) are also regulated by [Ca2+]1. The role of the arachidonic acid (AA) pathway in the Ca2+-dependent modulation of IM was investigated using whole-cell voltage clamp and intracellular perfusion in dissociated bullfrog sympathetic B neurons. 3. AA (6-120 ,uM) increased IM by about 50% of the control current in a Ca2+-dependent manner.4. Enhancements of IM by Ca2' and AA were blocked by the lipoxygenase (LO) inhibitors nordihydroguaiaretic acid (NDGA; 1-5 /uM) and 5,8,11-eicosatrynoic acid (ETI; 10 /UM). The cyclo-oxygenase inhibitor indomethacin (10 /uM) had no effect.

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Protein kinase C as mediator of arachidonic acid-induced decrease of neuronal M current

Cited by 22 publications

References 18 publications

Protein kinase C shifts the voltage dependence of KCNQ/M channels expressed in Xenopus oocytes

Protein kinase C shifts the voltage dependence of KCNQ/M channels expressed in Xenopus oocytes

Cholinergic Inhibition of Neocortical Pyramidal Neurons

Roles of arachidonic acid, lipoxygenases and phosphatases in calcium‐dependent modulation of M‐current in bullfrog sympathetic neurons.

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