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Carvacrol inhibits TRPM7‐like current in native myocytes from mesenteric artery of Hypertensive Rats
Author(s) -
Silva Darizy Flavia,
Reis Milena Ramos,
Vasconcelos Alyne Pereira,
Cruz Jader Santos,
Araújo Demetrius Antonio Machado
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.941.4
Subject(s) - carvacrol , trpm7 , chemistry , mesenteric arteries , extracellular , vascular smooth muscle , myocyte , medicine , endocrinology , ion channel , artery , smooth muscle , biochemistry , chromatography , receptor , essential oil
Carvacrol, a phenolic monoterpene, is found in several plants of Origanum genus and has been described to cause vasodilatation in mesenteric artery from normotensive rats by reducing Ca 2+ influx in vascular smooth muscle cells (VSMC). Then, the aim of this study was to investigate the effect of carvacrol on TRPM6/TRPM7 channels in VSMC from normotensive and hypertensive rats. Under whole‐cell voltage‐clamp, with voltage‐dependent Ca 2+ and K + channels blocked, currents generated by TRPM6/TRPM7 channels were measured by symmetrical voltage ramp commands to potentials between −100 to +100 mV, from a holding potential of 0 mV, displaying outward rectification in physiological extracellular medium. In VSMC isolated from hypertensive rats, carvacrol (100 and 300 μM) inhibit significantly both inward (−80 mV) and outward (+80 mV) currents [(current values at − 80 mV: (−3.42 ± 0.47 pA/pF; N = 5, control); (−1.07 ± 0.07 pA/pF, N = 5, p<0.05, carvacrol 100 μM); (−1.86 ± 0.34 pA/pF, N = 5, p<0.05, carvacrol 300 μM); (current values at + 80 mV: −6.21 ± 0.57 pA/pF, N = 5, control); (−3.53 ± 0.28 pA/pF, N = 5, p<0.01, carvacrol 100 μM); (−2.29 ± 0.27 pA/pF, N = 5, p<0.001, carvacrol 300 μM)]. This effect was similar to that induced by elevating extracellular Mg 2+ (2.5 mM, N=5). In the presence of 2‐APB (100 μM, N=5), a TRPM7 blocker, no additional effect in TRPM7/TRPM6 whole‐cell current was observed after perfusion with carvacrol (300 μM; N=5), suggesting that probably, the effect of carvacrol is through inhibition of TRPM7‐like currents (I TRPM7 ) in VSMC. Additionally, since the sensitivity of TRPM7 channels to Mg 2+ is an essential condition, we examined whether the above described current is inhibited by high concentrations of intracellular Mg 2+ . In this condition, the magnitude of TRPM7‐like current was significantly decreased inward and outward currents, in both myocytes, from hypertensive and normotensive rats, confirming that I TRPM were I TRPM6/TRPM7 . In conclusion, these data demonstrate that carvacrol inhibited I TRPM6/TRPM7 , in myocytes isolated from mesenteric artery of hypertensive and normotensive rats. This study provides the first electrophysiological evidence of TRPM7‐like current in native VSMC from mesenteric artery. Support or Funding Information Fundação de Amparo à pesquisa do estado da Bahia (FAPESB) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).