Potent perspectives of noble nanoparticles (NPs) for biomedical applications are well known but fundamental studies of their molecular interaction with target cell remain largely unexplored. Potassium channels play an important role in the membrane potential regulation in vascular smooth muscle (SM) cells and closely involved in vascular tone regulation. Voltage-gated ionic channels are expected to be modulated by plasmon resonance occurred on surface of gold nanoparticles (AuNPs) leading to alterations in their functionality but the amplitude and directionality of this effect need to be investigated. Colloidal AuNPs, having plasmon resonance of 525 nm, were synthesized by modified Turkevich method (2006) via reduction of sodium tetrachloroaurate by sodium ascorbate in aqueous solutions at room temperature. A dynamic light scattering study showed that AuNPs have average hydrodynamic size ~ of 5 nm core size and Zeta-potential of – 35 mV. Experimental design of the study comprised SM contractile recording combined with simultaneous fluorescent intracellular calcium concentration ([Ca2+]i) measurement in isolated rat aortic rings and ionic currents measuring in enzymatically isolated from rat aorta a single cells using patch clamp technique in whole-cell modification. When externally applied to the organ bath solution, AuNPs (10-6-10-4 M) decreased amplitude of norepinephrine-induced contractions in dose-dependent and endothelium-dependent manner but endothelium disruption did not abolished AuNPs-induced relaxation completely. AuNPs relaxed SM in the absence of decrease in [Ca2+]i. while [Ca2+]i in endothelial cells had increased. All cells demonstrated clearly expressed tail currents suggesting that the currents measured were mainly due to activation of outward potassium channels. Being added to the bath solution in doses close to EC50, AuNPs significantly increased whole cell peak K+ current density (IK) at + 70 mV from 33± 2pA/pF to 57±5 pA/pF (n=14, P < 0.05). Outward current oscillation associated probably with a MaxiK+ channels opening and correlated with [Ca2+]i were seen under AuNPs treatment. When irradiated by 5 mW/532 nm green laser to facilitate plasmon resonance, AuNPs significantly increased both the amplitude of maximal AuNPs-induced relaxation from 46.4±4.7% to 61.3±5.3% (n=10, P<0.05) and sensitivity of SM to AuNPs. Mean value of pD2 were 4.5±0.002 and 4.4±0.04, respectively (n=10, P<0.05). External irradiation increased AuNps-induced increment in IK from 57±5 pA/pF to 98±6 pA/pF (n=10, P < 0.05). In summary, plasmonic AuNPs are able to open K+- channels and relax SM in both endothelium-dependent and independent manner. One plausible explanation for AuNPs action is the interaction of the channel voltage sensors with local electric field on AuNPs surface. In case of laser irradiation this local electrical field enhanced due to local plasmon resonance which, in turn, increases IK and SM relaxation. In the absence of external irradiation such plasmon may be excited by natural tissue chemoluminescence in the presence of nonlinear effects on AuNPs surface. Of course, further research of AuNPs toxicity and functionality are necessary to create a safe and effective tool for pharmacological intervention which would be able to modulate IK but the data obtained clearly indicate that AuNPs possess the ability to initiate or facilitate K+ channel opening in vascular SM.