ArticleThe Journal of general physiology2009
Orientation of palmitoylated CaVbeta2a relative to CaV2.2 is critical for slow pathway modulation of N-type Ca2+ current by tachykinin receptor activation.
Article in The Journal of general physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- Molecular basis of the PIPeLife · 2022Article
- Four novel interaction partners demonstrate diverse modulatory effects on voltage-gated CaPflugers Archiv : European journal of physiology · 2019Article
- Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.Frontiers in physiology · 2017Review
- Phosphoinositides regulate ion channels.Biochimica et biophysica acta · 2015Review
- Voltage-dependent regulation of CaV2.2 channels by Gq-coupled receptor is facilitated by membrane-localized β subunit.The Journal of general physiology · 2014Article
- Ion channel regulation by protein S-acylation.The Journal of general physiology · 2014Review
- Ins and outs of T-channel structure function.Pflugers Archiv : European journal of physiology · 2014Review
- Regulation of Ca(V)2 calcium channels by G protein coupled receptors.Biochimica et biophysica acta · 2013Review
- Structure and function of the β subunit of voltage-gated Ca²⁺ channels.Biochimica et biophysica acta · 2013Review
- Stable incorporation versus dynamic exchange of β subunits in a native Ca2+ channel complex.Journal of cell science · 2013Article
- Membrane-localized β-subunits alter the PIP2 regulation of high-voltage activated Ca2+ channels.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Dual Regulation of Voltage-Sensitive Ion Channels by PIP(2).Frontiers in pharmacology · 2012Article
- Palmitoylation influences the function and pharmacology of sodium channels.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Ion channel regulation by protein palmitoylation.The Journal of biological chemistry · 2011Review
- Combined phosphoinositide and Ca2+ signals mediating receptor specificity toward neuronal Ca2+ channels.The Journal of biological chemistry · 2011Article
- Differential modulation of N-type calcium channels by micro-opioid receptors in oxytocinergic versus vasopressinergic neurohypophysial terminals.Journal of cellular physiology · 2010Article
- An oily competition: role of beta subunit palmitoylation for Ca2+ channel modulation by fatty acids.The Journal of general physiology · 2009Article
- The Ca2+ channel beta subunit determines whether stimulation of Gq-coupled receptors enhances or inhibits N current.The Journal of general physiology · 2009Article
- G protein modulation of CaV2 voltage-gated calcium channels.Channels (Austin, Tex.)Review
- Characterization of the gating brake in the I-II loop of CaV3 T-type calcium channels.Channels (Austin, Tex.)Review
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4 authors at 2 institutions in 1 country.
Funding
Abstract
The G(q)-coupled tachykinin receptor (neurokinin-1 receptor [NK-1R]) modulates N-type Ca(2+) channel (Ca(V)2.2 or N channel) activity at two distinct sites by a pathway involving a lipid metabolite, most likely arachidonic acid (AA). In another study published in this issue (Heneghan et al. 2009. J. Gen Physiol. doi:10.1085/jgp.200910203), we found that the form of modulation observed depends on which Ca(V)beta is coexpressed with Ca(V)2.2. When palmitoylated Ca(V)beta2a is coexpressed, activation of NK-1Rs by substance P (SP) enhances N current. In contrast, when Ca(V)beta3 is coexpressed, SP inhibits N current. However, exogenously applied palmitic acid minimizes this inhibition. These findings suggested that the palmitoyl groups of Ca(V)beta2a may occupy an inhibitory site on Ca(V)2.2 or prevent AA from interacting with that site, thereby minimizing inhibition. If so, changing the orientation of Ca(V)beta2a relative to Ca(V)2.2 may displace the palmitoyl groups and prevent them from antagonizing AA's actions, thereby allowing inhibition even in the presence of Ca(V)beta2a. In this study, we tested this hypothesis by deleting one (Bdel1) or two (Bdel2) amino acids proximal to the alpha interacting domain (AID) of Ca(V)2.2's I-II linker. Ca(V)betas bind tightly to the AID, whereas the rigid region proximal to the AID is thought to couple Ca(V)beta's movements to Ca(V)2.2 gating. Although Bdel1/beta2a currents exhibited more variable enhancement by SP, Bdel2/beta2a current enhancement was lost at all voltages. Instead, inhibition was observed that matched the profile of N-current inhibition from Ca(V)2.2 coexpressed with Ca(V)beta3. Moreover, adding back exogenous palmitic acid minimized inhibition of Bdel2/beta2a currents, suggesting that when palmitoylated Ca(V)beta2a is sufficiently displaced, endogenously released AA can bind to the inhibitory site. These findings support our previous hypothesis that Ca(V)beta2a's palmitoyl groups directly interact with an inhibitory site on Ca(V)2.2 to block N-current inhibition by SP.
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