Asunto(s)
Potenciales de Acción , Fascículo Atrioventricular/fisiopatología , Enfermedad por Depósito de Glucógeno de Tipo IIb/complicaciones , Frecuencia Cardíaca , Ventrículos Cardíacos/fisiopatología , Síndromes de Preexcitación/etiología , Adolescente , Estimulación Cardíaca Artificial , Análisis Mutacional de ADN , Técnicas Electrofisiológicas Cardíacas , Enfermedad por Depósito de Glucógeno de Tipo IIb/diagnóstico , Enfermedad por Depósito de Glucógeno de Tipo IIb/genética , Humanos , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Masculino , Mutación , Síndromes de Preexcitación/diagnóstico , Síndromes de Preexcitación/fisiopatología , Factores de Tiempo , Adulto JovenRESUMEN
1. It has been reported that allitridi, an active compound extracted from garlic, has many cardiovascular effects. However, it remains unknown whether allitridi affects major repolarization currents, such as the transient outward K(+) current (I(to) ), ultrarapid delayed rectifier K(+) current (I(Kur)) and the L-type Ca(2+) current (I(Ca)), in human atrial myocytes. 2. In the present study, we investigated the effects of allitridi on I(to), I(Kur), I(Ca) and the action potential in human isolated atrial myocytes using the whole-cell patch recording technique. 3. Allitridi reversibly inhibited I(to), but not I(Kur) and I(Ca), in human atrial myocytes. These effects of allitridi on I(to) were concentration dependent (IC(50) = 44.9 µmol/L). Inactivation of I(to) was accelerated and the voltage-dependent inactivation potential was shifted towards the negative direction. Allitridi (30 µmol/L) significantly prolonged action potential duration in human atrial myocytes. 4. The results of the present study indicate that allitridi inhibits I(to), but not I(Kur) and I(Ca), and prolongs the action potential duration in human atrial myocytes.
Asunto(s)
Compuestos Alílicos/farmacología , Atrios Cardíacos/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Canales de Potasio/efectos de los fármacos , Sulfuros/farmacología , Potenciales de Acción/efectos de los fármacos , Adulto , Anciano , Función Atrial/efectos de los fármacos , Fármacos Cardiovasculares/farmacología , Evaluación Preclínica de Medicamentos , Electrofisiología , Atrios Cardíacos/citología , Atrios Cardíacos/metabolismo , Humanos , Potenciales de la Membrana/efectos de los fármacos , Persona de Mediana Edad , Miocitos Cardíacos/fisiología , Canales de Potasio/metabolismoRESUMEN
1. Ketamine is widely used for the induction of anaesthesia in high-risk patients with cardiovascular instability or severe hypovolaemia. However, the ionic mechanisms involved in the effects of ketamine at therapeutically relevant concentrations in human cardiac myocytes are unclear. The present study was designed to investigate the effects of ketamine on L-type Ca2+ (I(Ca)), transient outward K+ (I(to)), ultra-rapid delayed rectifier K+ (I(Kur)) and inward rectifier potassium (I(K1)) currents, as well as on action potentials, in human isolated atrial myocytes. 2. Atrial myocytes were isolated enzymatically from specimens of human atrial appendage obtained from patients undergoing coronary artery bypass grafting. The action potential and membrane currents were recorded in both current- and voltage-clamp modes using the patch-clamp technique. 3. Ketamine inhibited I(Ca) with an IC(50) of 1.8 micromol/L. In addition, 10 micromol/L ketamine decreased the I(Ca) peak current at +10 mV from 5.1 +/- 0.3 to 2.1 +/- 0.4 pA/pF (P < 0.01), but did not change the threshold potential, peak current potential and reverse potential. 4. Ketamine had no effect on I(to), I(Kur) or I(K1), but it reversibly shortened the duration of the action potential in human atrial myocytes. 5. In conclusion, ketamine, at a clinically relevant concentration, shortens the action potential duration of the human atrial myocytes, probably by inhibiting I(Ca).