Role of cyclic amp dependent protein kinase in cannabinoid receptor modulation of potassium “A-current” in cultured rat hippocampal neurons

Hampson, Robert E.; Evans, Gareth J.; Mu, Jian; Zhuang, Shou-Yuan; King, Virginia C.; Childers, Steven R.; Deadwyler, Sam A.

doi:10.1016/0024-3205(95)00192-9

Cited by 64 publications

(36 citation statements)

References 13 publications

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“…With elevated levels of glutamate detected in epileptic tissue (Lothman et al, 1991), decreased release of this neurotransmitter would be a logical cannabinoid anticonvulsant mechanism. CB 1 receptor activation also increases the conductance of presynaptic A-type (Hampson et al, 1995) and G-proteincoupled inward rectifying K ϩ channels (Mackie et al, 1995). Increased K ϩ channel permeability attenuates neuronal bursting and stabilizes membrane potential, additional factors that would contribute to decreased epileptiform discharge.…”

Section: Discussionmentioning

confidence: 99%

The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy

Wallace

Blair²,

Falenski³

et al. 2003

J Pharmacol Exp Ther

358

307

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Several lines of evidence suggest that cannabinoid compounds are anticonvulsant. However, the anticonvulsant potential of cannabinoids and, moreover, the role of the endogenous cannabinoid system in regulating seizure activity has not been tested in an in vivo model of epilepsy that is characterized by spontaneous, recurrent seizures. Here, using the rat pilocarpine model of epilepsy, we show that the marijuana extract ⌬ 9 -tetrahydrocannabinol (10 mg/kg) as well as the cannabimimetic, 4, significantly increased both seizure duration and frequency. In some animals, CB 1 receptor antagonism resulted in seizure durations that were protracted to a level consistent with the clinical condition status epilepticus. Furthermore, we determined that during an short-term pilocarpine-induced seizure, levels of the endogenous CB 1 ligand 2-arachidonylglycerol increased significantly within the hippocampal brain region. These data indicate not only anticonvulsant activity of exogenously applied cannabinoids but also suggest that endogenous cannabinoid tone modulates seizure termination and duration through activation of the CB 1 receptor. Furthermore, Western blot and immunohistochemical analyses revealed that CB 1 receptor protein expression was significantly increased throughout the CA regions of epileptic hippocampi. By demonstrating a role for the endogenous cannabinoid system in regulating seizure activity, these studies define a role for the endogenous cannabinoid system in modulating neuroexcitation and suggest that plasticity of the CB 1 receptor occurs with epilepsy.

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Section: Discussionmentioning

confidence: 99%

The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy

Wallace

Blair²,

Falenski³

et al. 2003

J Pharmacol Exp Ther

358

307

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“…Activation of CB 1 receptors modulates various types of ion channels and enzymes in a cAMP-dependent or -independent manner. In neurons or CB 1 -transfected cells, application of a cannabinoid agonist activates A-type (198) and inwardly rectifying K ϩ channels (313) and inhibits N-and P/Q-type Ca 2ϩ channels (524) and D-and M-type K ϩ channels (365,466). The enzymes that are influenced by CB 1 activation include focal adhesion kinase (116), mitogen-activated protein kinase (460), phosphatidylinositol 3-kinase (45), and some enzymes involved in energy metabolism (190).…”

Section: A Intracellular Signaling Pathwaysmentioning

confidence: 99%

Endocannabinoid-Mediated Control of Synaptic Transmission

Kano¹,

Ohno‐Shosaku²,

Hashimotodani³

et al. 2009

Physiological Reviews

1,311

1,431

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The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB1 receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.

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“…CB 1 Rs are G protein-coupled receptors linked to pertussis-sensitive Gi/o α subunits. Activation of the α subunit triggers dissociation of the βγ complex, which reduces adenylate cyclase production of cyclic adenosine monophosphate [48], inhibits N-and P/Qtype voltage-gated calcium channels [31,[49][50][51][52], stimulates Atype potassium channels [53][54][55][56], activates G protein-coupled inwardly-rectifying potassium channels [57][58][59], and inhibits the vesicular release machinery [60]. These multiple mechanisms reduce presynaptic cell excitability and Ca 2+ , strongly diminishing presynaptic neurotransmitter release.…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Cannabinoids and Epilepsy

et al. 2015

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Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabisbased antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro-and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.

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Role of cyclic amp dependent protein kinase in cannabinoid receptor modulation of potassium “A-current” in cultured rat hippocampal neurons

Cited by 64 publications

References 13 publications

The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy

The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy

Endocannabinoid-Mediated Control of Synaptic Transmission

Cannabinoids and Epilepsy

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