Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes.

Lina T Al Kury,Uwe Ritter,Alexander V Zholos,Dimitrios Papandreou,Yuriy I Prylutskyy,Dariia O Dryn,Maxim O Platonov,Peter Scharff,Vasyl V Hurmach,Mariia I Melnyk

doi:10.3390/nano11123410

Abstract

Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecules, as they may interact with various biological macromolecules, including ion channels. To investigate the mechanisms of the inhibitory effects of SWCNTs on the muscarinic receptor cation current (mICAT), induced by intracellular GTPγs (200 μM), in isolated mouse ileal myocytes, we have used the patch-clamp method in the whole-cell configuration. Here, we use molecular docking/molecular dynamics simulations and direct patch-clamp recordings of whole-cell currents to show that SWCNTs, purified and functionalized by carboxylation in water suspension containing single SWCNTs with a diameter of 0.5–1.5 nm, can inhibit mICAT, which is mainly carried by TRPC4 cation channels in ileal smooth muscle cells, and is the main regulator of cholinergic excitation–contraction coupling in the small intestinal tract. This inhibition was voltage-independent and associated with a shortening of the mean open time of the channel. These results suggest that SWCNTs cause a direct blockage of the TRPC4 channel and may represent a novel class of TRPC4 modulators.

Highlights

Modeling of SWCNT Binding to TRPC4 Channel
To evaluate the possibility of SWCNT binding to the TRPC4 channel, we applied computer simulation techniques, namely, molecular docking and molecular dynamics (MD)
An SWCNT does not interact with each subunit of the TRPC4 channel. This SWCNT lies on its side, and one part partially sinks into the TRPC4 channel pore

Summary

Introduction

Single-walled carbon nanotubes (SWCNTs) have become a hot research area because of their unique physico-chemical properties and prospects for various applications in nanotechnology. Owing to their nanosize, good biocompatibility, stability and high reactivity, SWCNTs can be widely used in biomedicine [1,2,3]. It has been reported that SWCNTs penetrate the cells via endocytosis-dependent and independent pathways [4,5,6]. They can affect neuronal activity [7], most likely at the level of ion channels [8]. SWCNTs have been defined as neuroprotectors [9] and effective substrates for the culturing of neurons [10]

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Conclusion