Modulation of big K⁺ channel activity by ryanodine receptors and L‐type Ca²⁺ channels in neurons

Abstract

As metabotropic glutamate receptor type 1 (mGluR1) is known to couple L-type Ca2+ channels and ryanodine receptors (RyR, Chavis et al., 1996) in cerebellar granule cells, we examined if such a coupling could activate a Ca2+-sensitive K+ channel, the big K+ (BK) channel, in cultured cerebellar granule cells. We observed that (+/-)-1-amino-cyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) and quisqualate (QA) stimulated the activity of BK channels. On the other hand, (2S, 3S, 4S)-alpha-carboxycyclopropyl-glycine (L-CCG-I) and L-(+)-2-amino-4-phosphonobutyrate (L-AP4) had no effect on BK channels, indicating a specific activation by group I mGluRs. Group I mGluRs stimulation of the basal BK channel activity was mimicked by caffeine and both effects were blocked by ryanodine and nifedipine. Interestingly, carbachol stimulated BK channel activity but through a pertussis toxin (PTX)-sensitive pathway that was independent of L-type Ca2+ channel activity. Our report indicates that unlike the muscarinic receptors, group I mGluRs activate BK channels by mobilizing an additional pathway involving RyR and L-type Ca2+ channels.

Coassembly of Big Conductance Ca2+-activated K+ Channels and L-type Voltage-gated Ca2+ Channels in Rat Brain

“…Furthermore, studies with dual coupling of BK channels to both L-and N-type Ca 2ϩ channels have also been demonstrated, e.g. in neocortical pyramidal neurons (3,5,10). The discrepancy between studies reporting a functional BK/N-type coupling and the present data might be the result of several factors.…”

“…Such domains may consist of various membrane proteins, a number of scaffolding proteins, and different intracellular components with catalytical functions. As an example, in a series of studies Ca 2ϩ -activated potassium channels with big conductance (BK) 1 have been demonstrated to be functionally coupled to a number of other membrane proteins including voltage-gated Ca 2ϩ channels (1)(2)(3)(4)(5), cystic fibrosis transmembrane conductance regulator (6), Na ϩ /2Cl Ϫ /K ϩ cotransporters (7), glutamate phosphoinositide-coupled receptors (8), -type opioid receptors (9), ryanodine receptors (10,11), and N-methyl-D-aspartate receptors (12). These studies are all based on functional experiments.…”

Recurrent Dendrodendritic Inhibition of Accessory Olfactory Bulb Mitral Cells Requires Activation of Group I Metabotropic Glutamate Receptors

“…These changes include spatially localized increases in intracellular calcium via activation of ryanodine receptors (Chavis et al, 1996;Finch and Augustine, 1998;Takechi et al, 1998;del et al, 1999), up or downregulation of potassium and calcium conductances (Charpak et al, 1990;Schoppa and Westbrook, 1997;Chavis et al, 1998;Fagni et al, 2000;Heinbockel et al, 2006), and reduction in the strength of electrical synapses (Landisman and Connors, 2005). These cellular responses often serve to regulate network "tone" and modulate the propagation and extent of neural activity.…”

Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer

“…Rather, continued Nodal signalling in the epiblast is required for maintaining molecular pattern in the adjacent ExE. Previous studies demonstrate that Smad2-de®cient embryos express Nodal abundantly throughout the epiblast 11 . Interestingly, Bmp4 and Eomes (Fig.…”

“…Embryos lacking Nodal activity arrest shortly before gastrulation and fail to establish a primitive streak 8,9 . Smad2, an effector of Nodal signalling 10 , is also essential for establishment of the anterior±posterior axis 6,11 . It was important to compare the onset of patterning abnormalities in embryos lacking Nodal or Smad2.…”