 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, August 15, 2007, 27(33):8914-8926; doi:10.1523/JNEUROSCI.1739-07.2007
Previous Article | Next Article
Cellular/Molecular
Inositol Triphosphate-Mediated Ca2+ Signals Direct Purinergic P2Y Receptor Regulation of Neuronal Ion Channels
Oleg Zaika,1 Gleb P. Tolstykh,1 David B. Jaffe,2 andMark S. Shapiro1 1Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, and 2Department of Biology, Division of Life Sciences, The University of Texas at San Antonio, San Antonio, Texas 78249
Correspondence should be addressed to Mark S. Shapiro, Department of Physiology, MS 7756, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229. Email: shapirom{at}uthscsa.edu
Purinergic P2Y receptors are one of four types of Gq/11-coupled receptors in rat superior cervical ganglia (SCG) sympathetic neurons. In cultured SCG neurons, purinergic and bradykinin suppression of IM were similar in magnitude and somewhat less than that by muscarinic agonists. The effects of the P2Y receptor agonist UTP on neuronal excitability and discharge properties were studied. Under current clamp, UTP increased action potential (AP) firing in response to depolarizing current steps, depolarized the resting potential, decreased the threshold current required to fire an AP, and decreased spike-frequency adaptation. These effects were very similar to those resulting from bradykinin stimulation and not as profound as from muscarinic stimulation or full M-current blockade. We then examined the P2Y mechanism of action. Like bradykinin, but unlike muscarinic, purinergic stimulation induced rises in intracellular [Ca2+]i. Tests using expression of IP3"sponge" or IP3 phosphatase constructs implicated IP3 accumulation as necessary for purinergic suppression of IM. Overexpression of wild-type or dominant-negative calmodulin (CaM) implicated Ca2+/CaM in the purinergic action. Both sets of results were similar to bradykinin, and opposite to muscarinic, suppression. We also examined modulation of Ca2+ channels. As for bradykinin, purinergic stimulation did not suppress ICa, unless neuronal calcium sensor-1 (NCS-1) activity was blocked by a dominant-negative NCS-1 construct. Our results indicate that P2Y receptors modulate M-type channels in SCG cells via IP3-mediated [Ca2+]i signals in concert with CaM and not by depletion of phosphatidylinositol-4, 5-biphosphate. We group purinergic P2Y and bradykinin B2 receptors together as having a common mode of action.
Key words: M current; calcium channel; purinergic receptor; PLC signaling; G-protein; patch clamp; sympathetic neuron
Received April 17, 2007; revised June 28, 2007; accepted June 30, 2007.
Correspondence should be addressed to Mark S. Shapiro, Department of Physiology, MS 7756, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229. Email: shapirom{at}uthscsa.edu
This article has been cited by other articles:
B. Liu, H. Liang, L. Liu, and H. Zhang
Phosphatidylinositol 4,5-bisphosphate hydrolysis mediates histamine-induced KCNQ/M current inhibition
Am J Physiol Cell Physiol, July 1, 2008; 295(1): C81 - C91.
[Abstract] [Full Text] [PDF]
Z. Jia, J. Bei, L. Rodat-Despoix, B. Liu, Q. Jia, P. Delmas, and H. Zhang
NGF Inhibits M/KCNQ Currents and Selectively Alters Neuronal Excitability in Subsets of Sympathetic Neurons Depending on their M/KCNQ Current Background
J. Gen. Physiol., May 26, 2008; 131(6): 575 - 587.
[Abstract] [Full Text] [PDF]
M. Bal, O. Zaika, P. Martin, and M. S. Shapiro
Calmodulin binding to M-type K+ channels assayed by TIRF/FRET in living cells
J. Physiol., May 1, 2008; 586(9): 2307 - 2320.
[Abstract] [Full Text] [PDF]
C. C. Hernandez, O. Zaika, G. P. Tolstykh, and M. S. Shapiro
Regulation of neural KCNQ channels: signalling pathways, structural motifs and functional implications
J. Physiol., April 1, 2008; 586(7): 1811 - 1821.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|