Biological pacemaker

Cardiac arrhythmias are common diseases which include complex and multifactorial disorders of cardiac rhythm. Severe bradycardia (i.e. slowing of heart rate) and atrio-ventricular node block often require implantation of an electronic pacemaker as the only possible therapy. The aim of this project is to create a cellular substrate able to autonomously generate rhythmic, spontaneous activity and to ... read more

Genetics of pacemaker channel diseases

Cardiac pathologies associated with rhythm disorders represent one of the major causes of morbidity and mortality in western countries. In the last few years, molecular approaches to cardiovascular research have identified many genetic defects leading to alterations of the cardiac function. Recent work from our group has identified a mutation (S672R) in the hHCN4 gene, a human isoform of the pacemaker channel gene, which is ... read more

Pharmacology of the pacemaker channel

Drugs able to selectively block f-channels have a potential therapeutic use in those cases where it is useful to slow heart rate without altering other cardiovascular functions such as the ventricular contractility. Several molecules able to block the pacemaker f-channels such as zetabradine, ZD7288 and ivabradine have been developed in the past, but only ivabradine has passed all clinical trials and is now marketed as an antianginal drug in ... read more

Funny current

Cardiac rhythmic activity is generated by "pacemaker" cells, which in mammals are located in the sino-atrial node (SAN). Action potentials of SAN cells have a special phase, called diastolic (or pacemaker) depolarization: at the end of an action potential, the pacemaker depolarization slowly takes the membrane voltage up to threshold for firing of a new action potential, thus generating repetitive activity. What is the mechanism ... read more