Electrophysiological alterations in human cardiac myocytes: new targets for pharmacological interventions.

The electrophysiological properties of single human ventricular and atrial myocytes have been studied using the patch-clamp technique. Ventricular myocytes isolated from explanted human failing hearts consistently show the occurrence of the pacemaker current If, whose electrophysiologic and pharmacological properties resemble those of the f channel expressed in cardiac pacemakers. If is almost fully activated by negative steps close to the physiological resting potential, is increased by catecholamines through the stimulation of ß-adrenoceptors and is use-dependently blocked by zatebradine. Interestingly, the density and maximal specific conductance of this current is significantly higher in myocytes from ischemic cardiomyopathic hearts than in control or dilated cardiomyopathic hearts, thus suggesting that the etiology of the disease may influence the over-expression of the f channel. Even if the mechanism underlying this phenomenon is unknown, recent data obtained in a rat model of myocardiac hypertrophy and failure suggest that angiotensin II may play a relevant role. If is constitutionally expressed in the majority of atrial myocytes isolated from normal human right appendages; at variance with ventricular cells, its activation occurs at voltages more negative than the physiological resting potential of atrial cells. However, both ß-adrenoceptor and 5HT4-receptor stimulation may shift the activation curve of If, thus increasing its contribution to the diastolic phase of the atrial action potential. If may represent an arrhythmogenic mechanism in human cells; thus, pharmacological interventions able to prevent disease-induced over-expression of the channel, to antagonize catecholamine or serotonin stimulation of its activation or to selectively block the channel may act as antiarrhythmic agents in heart disease.