Calcium-Activated Potassium Channels Are Selectively Coupled to P/Q-Type Calcium Channels in Cerebellar Purkinje Neurons

Womack, Mary D.; Chevez, Carolyn; Khodakhah, Kamran

doi:10.1523/jneurosci.2915-04.2004

Cited by 173 publications

(174 citation statements)

References 35 publications

Supporting

Mentioning

166

Contrasting

Order By: Relevance

“…Note the change of the action potential waveform. WIN 55,212-2 caused a decrease in the afterhyperpolarization amplitude, similar to that seen after block of calcium-activated potassium channels and block of P/Q-type channels (Womack et al 2004). B: bar graphs comparing average firing rates under control conditions and in the presence of WIN 55,212-2 for 4 Purkinje neurons.…”

Section: Discussionmentioning

confidence: 67%

“…P-type Ca 2ϩ channels have been shown to play an important role in eliciting repetitive firing. According to Womack et al (2004), blocking only half of the P/Q-type voltagegated calcium channels (corresponding to removal of 25% of total action potential-evoked calcium entry) caused a significant increase in the rate and decrease in the regularity of Purkinje neuron spontaneous firing via decreased recruitment of calcium-activated potassium channels (Womack et al 2004). Therefore we expected that inhibition of P current by WIN 55,212-2 should increase the firing rate.…”

Section: Win 55212-2 Increases the Firing Rate Of Spontaneous Firingmentioning

confidence: 99%

See 1 more Smart Citation

Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons

Fisyunov¹,

Tsintsadze²,

Min³

et al. 2006

Journal of Neurophysiology

View full text Add to dashboard Cite

Fisyunov, Alexander, Vera Tsintsadze, Rogier Min, Nail Burnashev, and Natalia Lozovaya. Cannabinoids modulate the P-type high-voltage-activated calcium currents in Purkinje neurons. J Neurophysiol 96: 1267-1277, 2006. First published May 31, 2006 doi:10.1152/jn.01227.2005. Endocannabinoids released by postsynaptic cells inhibit neurotransmitter release in many central synapses by activating presynaptic cannabinoid CB1 receptors. In particular, in the cerebellum, endocannabinoids inhibit synaptic transmission at granule cell to Purkinje cell synapses by modulating presynaptic calcium influx via N-, P/Q-, and R-type calcium channels. Using whole cell patch-clamp techniques, we show that in addition to this presynaptic action, both synthetic and endogenous cannabinoids inhibit P-type calcium currents in isolated rat Purkinje neurons independent of CB1 receptor activation. The IC 50 for the anandamide (AEA)-induced inhibition of P-current peak amplitude was 1.04 Ϯ 0.04 M. In addition, we demonstrate that all the tested cannabinoids in a physiologically relevant range of concentrations strongly accelerate inactivation of P currents. The effects of AEA cannot be attributed to the metabolism of AEA because a nonhydrolyzing analogue of AEA, methanandamide inhibited P-type currents with a similar efficacy. All effects of cannabinoids on P-type Ca 2ϩ currents were insensitive to antagonists of CB1 cannabinoid or vanilloid TRPV1 receptors. In cerebellar slices, WIN 55,212-2 significantly affected spontaneous firing of Purkinje neurons in the presence of CB1 receptor antagonist, in a manner similar to that of a specific P-type channel antagonist, indicating a possible functional implication of the direct effects of cannabinoids on P current. Taken together these findings demonstrate a functionally important direct action of cannabinoids on P-type calcium currents.

show abstract

Section: Discussionmentioning

confidence: 67%

Section: Win 55212-2 Increases the Firing Rate Of Spontaneous Firingmentioning

confidence: 99%

Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons

Fisyunov¹,

Tsintsadze²,

Min³

et al. 2006

Journal of Neurophysiology

View full text Add to dashboard Cite

show abstract

“…In cerebellar Purkinje cells expressing no functional NMDARs, the activation of SK channels seems to require Ca 2ϩ influx through P͞Q-type voltage-gated Ca 2ϩ channels (30). In the triplet, NMDAR could be replaced by a certain set of cell surface Ca 2ϩ channels.…”

Section: Discussionmentioning

confidence: 99%

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Moriguchi

Nishi

Komazaki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Junctional membrane complexes (JMCs) composed of the plasma membrane and endoplasmic͞sarcoplasmic reticulum seem to be a structural platform for channel crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the sarcoplasmic reticulum membrane and binding with the plasma membrane in muscle cells. In this article, we report that mutant JP double-knockout (JP-DKO) mice lacking neural JP subtypes exhibited an irregular hindlimb reflex and impaired memory. Electrophysiological experiments indicated that the activation of small-conductance Ca 2؉ -activated K ؉ channels responsible for afterhyperpolarization in hippocampal neurons requires endoplasmic reticulum Ca 2؉ release through ryanodine receptors, triggered by NMDA receptor-mediated Ca 2؉ influx. We propose that in JP-DKO neurons lacking afterhyperpolarization, the functional communications between NMDA receptors, ryanodine receptors, and small-conductance Ca 2؉ -activated K ؉ channels are disconnected because of JMC disassembly. Moreover, JP-DKO neurons showed an impaired long-term potentiation and hyperactivation of Ca 2؉ ͞calmodulin-dependent protein kinase II. Therefore, JPs seem to have an essential role in neural excitability fundamental to plasticity and integrated functions.hippocampus ͉ learning and memory ͉ long-term potentiation ͉ ryanodine receptor ͉ SK channel F unctional communication between cell-surface and intracellular channels is an essential feature of excitable cells (1). During initiation of contraction in striated muscle cells, the activation of cell-surface dihydropyridine receptor (DHPRs) channels opens ryanodine receptors (RyRs) and triggers Ca 2ϩ release from the sarcoplasmic reticulum via either the ''Ca 2ϩ -induced Ca 2ϩ release'' or the ''voltage-induced Ca 2ϩ release'' mechanism (2). The functional couplings between the channels take place in junctional membrane complexes (JMCs), designated as the ''triad junction'' in skeletal muscle, ''diad'' in cardiac muscle, and ''peripheral coupling'' in immature striated and smooth muscles (3, 4). Recent studies indicated that junctophilin (JP) subtypes, namely JP-1-JP-4, contribute to JMC formation in muscle cells (5, 6). In JP-1 knockout mice with perinatal lethality, mutant skeletal muscle shows deficiency of triad junctions and insufficient contraction probably caused by impaired communication between DHPRs and RyRs (7). In JP-2 knockout embryos showing cardiac arrest, mutant cardiac myocytes exhibit deficiency of peripheral couplings and arrhythmic Ca 2ϩ signaling probably caused by functional uncoupling between DHPRs and RyRs (5). In the brain, both JP-3 and JP-4 are expressed in similar discrete neuronal sites and may collaboratively contribute to JMC formation (8, 9). However, the role of neural JP subtypes is largely unknown. Using knockout mice lacking both JP-3 and JP-4 (JP-DKO mice), we report their essential contributions to the tuning of excitability and plasticity in hippocampal pyramidal neurons. ResultsGeneration of JP-DKO Mice Bearing Lethality. JP-4 knockou...

show abstract

“…Current was injected to achieve a membrane potential of approximately Ϫ55 mV, a value that under our experimental conditions approximates the average potential between action potentials in spontaneously firing Purkinje cells (Womack et al, 2004). A patch of granule cells beneath the Purkinje cell was then electrically activated at various stimulation intensities.…”

Section: The Input-output Function Of Purkinje Cells Is Independent Omentioning

confidence: 99%

The Linear Computational Algorithm of Cerebellar Purkinje Cells

Walter¹,

Khodakhah²

2006

J. Neurosci.

View full text Add to dashboard Cite

The orchestration of simple motor tasks by the cerebellum results in coordinated movement and the maintenance of balance. The cerebellum integrates sensory and cortical information to generate the signals required for the coordinated execution of simple motor tasks. These signals originate in the firing rate of Purkinje cells, each of which integrates sensory and cortical information conveyed by granule cell synaptic inputs. Given the importance of the granule cell input-Purkinje cell output function for cerebellar computation, this algorithm was determined. Using several stimulation paradigms, including those that mimicked patterns of granule cell activity similar to those observed in vivo, we quantified the poststimulus maximum firing rate and number of extra spikes in response to granule cell synaptic input. Both of these parameters linearly encoded the strength of synaptic input when inhibitory synaptic transmission was blocked. This linear algorithm was independent of the location or temporal pattern of synaptic input. With inhibitory synaptic transmission intact, the maximum firing rate, but not the number of extra spikes, encoded the strength of granule cell synaptic input. Furthermore, the maximum firing rate of Purkinje cells linearly encoded the strength of synaptic input whether or not the activation of granule cells resulted in a pause in Purkinje cell firing. On the basis of the data presented, we propose that Purkinje cells encode the strength of granule cell synaptic input in their maximum firing rate with a linear algorithm.

show abstract

Calcium-Activated Potassium Channels Are Selectively Coupled to P/Q-Type Calcium Channels in Cerebellar Purkinje Neurons

Cited by 173 publications

References 35 publications

Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons

Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

The Linear Computational Algorithm of Cerebellar Purkinje Cells

Contact Info

Product

Resources

About

Calcium-Activated Potassium Channels Are Selectively Coupled to P/Q-Type Calcium Channels in Cerebellar Purkinje Neurons

Cited by 173 publications

References 35 publications

Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons

Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons

Functional uncoupling between Ca 2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

The Linear Computational Algorithm of Cerebellar Purkinje Cells

Contact Info

Product

Resources

About

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins