EC Pharmacology and Toxicology

It was established that plasmonic gold nanoparticle (Au NPs) possess the ability to open Maxi-K (BKCa) channels in smooth muscle (SM) cells obtained from different tissues in a remote-control manner. The aim of this study was also to clarify the intrinsic mechanisms of this type channels activation in myocytes isolated from rat pulmonary artery and mouse ileum were recorded in the whole-cell and cell-attached configurations of the patch-clamp techniques and changes intracellular calcium concentration ([Ca²⁺]_i) were monitored using confocal microscopy. First of all we have compared the effects of AuNPs on Maxi-K channel activity under weak and strong intracellular Ca²⁺ buffering (Ca²⁺ “clamp” at 100 nM). When weak Ca²⁺ buffering, Maxi-K current density was increased by AuNPs applied, and then further increased by green laser irradiation (GLI, 5 mW, 532 nm). The potentiating effect of AuNPs alone was due to an increase in maximal conductance (Gmax) by about 50% without any shift of the activation curve of K⁺ conductance. GLI in the presence of AuNPs produced an additional effect increasing the maximal K⁺ conductance, but instead shifted the potential of half-maximal activation (V1/2) value negatively by about 10 mV. In contrast, under conditions of strong intracellular Ca²⁺ buffering, no effect of AuNPs alone or AuNPs/GLI on Maxi-K currents was observed. It is clear that the effects of AuNPs/GLI were due to a significant increase in channel open probability, while single channel conductance remained unchanged. It is interesting that the deviation from independence of channel gating was observed, suggesting that surface plasmon resonance may not similarly affect all channels present in the membrane patch. This type of regulation is fundamentally different from other common types of drug action. We conclude that AuNPs activate Maxi-K channels via both Gmax increase and a negative V1/2 shift. Moreover, this channel opening effect of AuNPs/GLI is clearly calcium-dependent, as they are able to produce oscillations in [Ca²⁺]_i and it could be completely abolished by “clamping” the intracellular Ca²⁺ concentration.

Keywords: Plasmon; Gold Nanoparticles; Ion Channels; Smooth Muscle (SM); Ca²⁺ Buffering; [Ca²⁺]_i

1. Soloviev A., et al. “Plasmonic gold nanoparticles as a potent potassium channel opener inn vascular smooth muscle cells”. Proceed. IUPS Congr., Birmingham, UK (2013): 80.
2. Soloviev A., et al. “Plasmonic gold nanoparticles possess the ability to open potassium channels in rat thoracic aorta smooth muscle in a remote control manner”. Vascular Pharmacology 72 (2015): 190-196.
3. Dykman L and Klebtsov N. “Gold nanoparticles in biomedical applications; recent advances and perspectives”. Chemical Society Reviews 41 (2012): 2256-2282.
4. Jacak W., et al. “On the size difference and spatial range for the plasmon effect in photovoltaic efficiency enhancement”. Solar Energy Materials and Solar Cells 147 (2016): 1-16.
5. A Soloviev., et al. “Non-drug remote control of Maxi-K channels in smooth muscle cells with nsano-photonic stimuli using plasmonic gold nanoparticles”. JSM Nanotechnology and Nanomedicine1 (2016): 1-10.
6. Lugo K., et al. “Remote switching of cellular activity and cell signaling using light in conjunction with quantum dots”. Biomed Optics Express 3 (2012): 447-454.