The contraction of vascular smooth muscle cells (VSMCs) is critically dependent on the intracellular calcium concentration [Ca2+]i. Relevant mechanisms contributing to tight control of [Ca2+]i include L-type calcium channels (LTCCs), ryanodine receptor channels (RyR), resting membrane potential (Em) and large-conductance Ca2+-activated K+ channels (BK). The increased vascular tone that defines essential hypertension associates to depolarisation of VSMCs. In hypertensive rat models, it has been postulated that depolarization-induced increased expression of α1C subunit of LTCCs leads to elevated basal [Ca2+]i. However, it is unclear whether this mechanism contributes to the genesis and maintenance of essential hypertension, as these models show blood pressure values closed to hypertensive crisis. We have use a genetic mouse model of essential hypertension with moderate blood pressure increase (BPH mice) and its normotensive controls (BPN) to study the functional expression of LTCCs in mesenteric arteries VSMCs. Animal protocols were approved by the Institutional Care and Use Committee of our Institution. Mice were killed by decapitation after isofluorane anaesthesia (5% at 2.5 l min-1 O2), and mesenteric VSMCs were obtained by enzymatic dissociation. Expression and function of LTCCs in VSMCs form BPN and BPH VSMCs were explored with real-time PCR, electrophysiological recordings and observation of calcium influx “sparklets” with total internal reflection fluorescence (TIRF) microscopy . qPCR showed a decreased expression of α1C and β2 mRNA and a significant increase in the α2δ subunit in BPH VSMCs. Moreover, LTCCs currents recorded in BPH had a significantly reduced density. Also LTCCs from BPH cells were more sensitive to 5µM BayK 8644 and were differentially modulated by 100 µM gabapentin (GBP), a ligand of α2δ subunits, suggesting a different molecular composition of LTCCs. To test this hypothesis, the effect of GBP was explored in HEK cells transfected with different LTCCs subunits. GBP dose-response relationship indicated similarities between α1C+α2δ+β2 transfected HEK and BPH and between α1C+α2δ and BPN. Organization of the LTCCs was studied by TIRF. LTCCs clusters operating in the high open probability mode were significant larger in BPH mice, and sparklets amplitude histograms indicates that LTCCs clusters in BPH are composed of a larger number of channels. In conclusion, we found a decreased mRNA expression and a lower LTCCs current density in BPH. However, LTCCs cluster from BPH were larger and showed higher activity at rest. We postulated that changes in the subunit composition of LTCCs in BPH VSMCs could account for these differences.