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) current, first described almost 30 years ago in sinoatrial node (SAN) myocytes, is a mixed sodium/potassium inward current, activated on hyperpolarisation in the diastolic range of voltages.‘Funny’ () channels are activated by intracellular cyclic adenosine monophosphate (c AMP) concentrations according to a mechanism mediating regulation of heart rate by the autonomic nervous system, as well as by voltage hyperpolarisation.
Clearly, therefore, independent reduction of heart rate, through inhibition of the I current, appears to be a suitable therapeutic option for patients with ischaemic heart disease.β-Adrenoceptor antagonists (β-blockers) reduce intracellular c AMP levels, and a substantial part of their negative chronotropic effect is therefore attributable to a reduction of the I channel antagonists, both of which have traditionally been used to reduce myocardial ischaemia, are ‘pure’ heart rate-lowering drugs.
These agents may, in fact, have adverse cardiovascular and noncardiovascular effects.
Conversely, the novel heart rate-reducing agent ivabradine is a specific blocker of current-regulated steepness of the diastolic depolarisation in SAN myocytes, thereby increasing diastolic duration, without altering action potential duration or causing negative inotropy.
As such, ivabradine is particularly useful in patients with chronic stable angina pectoris.
Further clinical studies are ongoing to evaluate the efficacy of ivabradine in patients with coronary heart disease, left ventricular dysfunction and heart failure.
This short article reviews the current state of knowledge of the properties of the ‘funny’ current in relation to exploitation of the IThe preparation of this manuscript was supported by Servier.
Professor Di Francesco wishes to declare that Servier has provided support for research activity in his laboratory.
Professor Borer is a paid consultant to Servier Laboratoires, the manufacturer of ivabradine.
Editorial support for the preparation of the manuscript was provided by Wolters Kluwer Health Medical Communications.Tags: Adult Dating, affair dating, sex dating