title: Geraniol blocks calcium and potassium channels in the mammalian myocardium: useful effects to treat arrhythmias.
abstract: Geraniol is a monoterpene present in several essential oils, and it is known to have a plethora of pharmacological activities. In this study, we explored the contractile and electrophysiological properties of geraniol and its antiarrhythmic effects in the heart. The geraniol effects on atrial contractility, L-type Ca(2+) current, K(+) currents, action potential (AP) parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated. In the atrium, geraniol reduced the contractile force (~98%, EC = 1,510 ± 160 μM) and diminished the positive inotropism of CaCl2 and BAY K8644. In cardiomyocytes, the IC a,L was reduced by 50.7% (n = 5) after perfusion with 300 μM geraniol. Moreover, geraniol prolonged the AP duration (APD) measured at 50% (n = 5) after repolarization, without changing the resting potential. The increased APD could be attributed to the blockade of the transient outward K(+) current (Ito ) (59.7%, n = 4), the non-inactivation K(+) current (Iss ) (39.2%, n = 4) and the inward rectifier K(+) current (IK 1 ) (33.7%, n = 4). In isolated hearts, geraniol increased PRi and QTi without affecting the QRS complex (n = 6), and it reduced both the left ventricular pressure (83%) and heart rate (16.5%). Geraniol delayed the time to onset of ouabain-induced arrhythmias by 128%, preventing 30% of the increase in resting tension (n = 6). Geraniol exerts its negative inotropic and chronotropic responses in the heart by decreasing both L-type Ca(2+) and voltage-gated K(+) currents, ultimately acting against ouabain-induced arrhythmias.
authors.affiliation: Laboratory of Biophysics Heart, Department of Physiology, Federal University of Sergipe, Sao Cristovao, Brazil.
authors.forename: José Evaldo Rodrigues
authors.initials: JE
authors.lastname: de Menezes-Filho
authors.forename: Antônio Nei Santana
authors.initials: AN
authors.lastname: Gondim
authors.forename: Jader Santos
authors.initials: JS
authors.lastname: Cruz
authors.forename: Américo Azevedo
authors.initials: AA
authors.lastname: de Souza
authors.forename: José Nilson Andrade Dos
authors.initials: JN
authors.lastname: Santos
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Conde-Garcia
authors.forename: Damião Pergentino
authors.initials: DP
authors.lastname: de Sousa
authors.forename: Michel Santana
authors.initials: MS
authors.lastname: Santos
authors.forename: Evaleide Diniz
authors.initials: ED
authors.lastname: de Oliveira
authors.forename: Carla Maria Lins
authors.initials: CM
authors.lastname: de Vasconcelos
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015220:Calcium Channels; D004562:Electrocardiography / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D013729:Terpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000080462:Acyclic Monoterpenes; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D013729:Terpenes; C007836:geraniol