Every organism needs molecular antennae in order to sense the environmental temperature. In mammals, these antennae are a set of ion channels called thermo Transient Receptor Potential (thermoTRP). TRPV1 is a heat activated channel that belongs to TRP family, with an activation threshold around 42 °C. Experimental evidences show that TRPV1 posses a similar structural architecture to voltage-dependent K+ channels (Kv). Nevertheless, TRPV1 has a weakly voltage dependence (number of apparent gating charges, z = 0.83 e0) and in contrast with the numerous positively charged residues contained in the S4 of Kv channels (∼12 e0 gating charges/channel), it has only one arginine (R557) located in the fourth transmembrane segment (S4). However, the molecular determinant that confers the voltage sensitivity to this channel remains elusive. using site-directed mutagenesis we have neutralized several charged amino acid (positives and negatives) along to the channel. The electrophysiological studies (macro-patch in X. laevis oocytes), surprisingly reveals that the uncharged S4 TRPV1 channels still conserve the same voltage dependence as wt channels. Furthermore, neutralizations in other transmembrane segments or even neutralizations on the pore region do not affect the voltage sensitivity of TRPV1 channels. Despite the weak voltage dependence of TRPV1 channel, the membrane voltage has a huge impact over the temperature activation; changing the activation enthalpy and the ionic current kinetics. At hyperpolarizing potentials the temperature activation shows a delay resembling the Cole-Moore shift. Furthermore, at depolarizing potential the channel kinetics speeds up, revealing an allosteric connection between voltage and thermal stimuli. This work was supported by Fondecyt grant 1110430 to RL, Fondecyt 1120802 to CG and ACT 10224 to CG. CINV is a Scientific Millennium Institute.