In this work, we introduce the use of an electrochemical sensor based on ion-channel mechanism in order to investigate the interaction between different-functionalized calixarene mercaptoalkyl derivatives and dopamine at the aqueous/organic interface. Three different calix[4]arene derivatives, functionalized with mercaptoalky groups at the upper-rim of calix[4]arene, were synthesized, and their structures were characterized by FTIR, ¹H and ¹³C NMR spectroscopy, and elemental analysis techniques. Moreover, these calixarene-mercaptoalkyl derivatives were grafted onto gold electrode surface by covalent Au-S bound. To elucidate the functional groups' influences on the signal generation mechanism, three different-substituted calixarene-mercaptoalkyl derivatives, with an opposite arrangement of the functional moieties and mercaptoalkyl groups at the lower and the upper rim of the calixarene, were interacted for the first time with dopamine. The formation of a supramolecular complex between the calix[4]arene host and the dopamine guest were confirmed by Osteryoung square-wave voltammetry with [Ru(NH<inf>3</inf>)<inf>6</inf>]Cl<inf>3</inf> as an redox active marker. The proposed electrochemical sensors were suitable for the determination of dopamine in the concentration range from 1.0 × 10^-11 M to 1.0 × 10^-6 M. In order to demonstrate the applicability of the sensors proposed, the electrochemical determination of dopamine in the presence of ascorbic acid and uric acid were checked. It was proved that these interferences did not influence on dopamine determination. The detection limit was estimated as 4.9 pM.