Elevation of cytosolic calcium by cholinoceptor agonists in SH-SY5Y human neuroblastoma cells: estimation of the contribution of voltage-dependent currents

Content Provider	Scilit
Author	Forsythe, Ian D. Lambert, David G. Nahorski, Stefan R. Linsdell, Paul
Copyright Year	1992
Description	Journal: British Journal of Pharmacology 1 Muscarinic but not nicotinic receptor stimulation in SH-SY5Y human neuroblastoma cells induces a concentration-dependent increase in $[^{3}$H]-inositol phosphate formation and a biphasic increase in [Ca^{2+}$]_{i}$. The latter involves release from both an intracellular store and $Ca^{2+}$ entry across the plasma membrane. Here we examine the possibility that this agonist-stimulated $Ca^{2+}$ entry occurs indirectly, as a consequence of depolarization. 2 Electrophysiological characterization, by whole cell patch-clamp techniques revealed that SH-SY5Y cells possess a tetrodotoxin-sensitive inward sodium current, a dihydropyridine-insensitive calcium current and an outward potassium current which was blocked by tetraethylammonium, 4-aminopyridine and intracellular caesium ions. The outward potassium current showed voltage-dependent activation and inactivation, similar to that seen for A-currents. 3 Application of nicotinic agonists evoked an inward current in cells voltage-clamped at negative holding potentials, but this current rectified, resulting in little or no outward current flow at positive potentials. The mean amplitude at a holding potential of — 60 mV was — 1.14 nA. Extrapolation of the current-voltage relation gave a reversal potential of +8mV, indicative of a non-specific cationic permeability. 4 Application of muscarinic agonists had no detectable effect in most of the cells tested. However, in one third of cells studied, a small slowly activating inward current was observed. The mean amplitude of this current at a holding potential of — 60 mV was — 8.3 pA. 5 This study confirms that SH-SY5Y cells possess voltage-dependent sodium, potassium and calcium currents. In addition, these cells are strongly depolarized by nicotinic agonists, which produce little change in [Ca^{2+}$]_{i}$. On the other hand, muscarinic agonists produce profound changes in [Ca^{2+}$]_{i}$ with only a small inward current (depolarization). The contrasting effects of these two cholinoceptor agonists strongly implies that the $Ca^{2+}$ entry after muscarinic receptor activation is not primarily due to activation of voltage-dependent calcium channels.
Related Links	http://europepmc.org/articles/pmc1907587?pdf=render https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1992.tb14488.x
Ending Page	214
Page Count	8
Starting Page	207
e-ISSN	14765381
DOI	10.1111/j.1476-5381.1992.tb14488.x
Journal	British Journal of Pharmacology
Issue Number	1
Volume Number	107
Language	English
Publisher	Wiley-Blackwell
Publisher Date	1992-09-01
Access Restriction	Open
Subject Keyword	Journal: British Journal of Pharmacology Sh-sy5y Human Neuroblastoma Inositol Phosphates Muscarinic Receptors Nicotinic Receptors Potassium Current
Content Type	Text
Resource Type	Article