Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 'funny' (pacemaker, I(f)) 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' (f) channels are activated by intracellular cyclic adenosine monophosphate (cAMP) concentrations according to a mechanism mediating regulation of heart rate by the autonomic nervous system, as well as by voltage hyperpolarisation. Structural subunits of native f-channels are the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels; of the four HCN isoforms known, HCN4 is the most highly expressed in SAN tissue. The I(f) current is a natural target in the search for drugs aimed specifically at affecting heart rate, given its function in pacemaking. Increased heart rate has a negative influence on clinical outcome in patients with cardiovascular disease, and indeed is also an established risk factor for cardiovascular and all-cause mortality in the general population. Clearly, therefore, independent reduction of heart rate, through inhibition of the I(f) current, appears to be a suitable therapeutic option for patients with ischaemic heart disease.beta-Adrenoceptor antagonists (beta-blockers) reduce intracellular cAMP levels, and a substantial part of their negative chronotropic effect is therefore attributable to a reduction of the I(f) current. However, neither beta-blockers nor Ca(2+) 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 f-channels, hence a selective inhibitor of the pacemaker I(f) current in the SAN. Ivabradine slows heart rate by reducing the I(f) 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 I(f) function in pacemaking generation and modulation for the pharmacological control of heart rate.
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PMID:The funny current: cellular basis for the control of heart rate. 1799 60

Disturbance of cardiac rhythm is one of the consequences of myocardial ischemia/reperfusion injury. Many researchers have prompted considerable interests in developing therapeutic approaches for its control. In present study, we want to determine whether that adenosine pre- and postconditioning have protective effects on sinoatrial node ischemia/reperfusion injury on morphology, arrhythmia score, serological markers (CK-MB and cTnT), SOD activities, MDA levels and expression of HCN4 channels in SA node cells. According to the arrhythmia score recorded, whether adenosine used in terms of ischemia or reperfusion, the total number of arrhythmia was significantly reduced, as well as the number of its episodes was also markedly decreased. We have also shown a clear correlation between HCN4 channels expression and the dysfunction of SA node cells. HCN4 immunoreactivity decreased after adenosine pre- and postconditioning, but changes were significantly smaller in the cells of the SA node compared with cells of I/R group. The content of cTnT, CK-MB and MDA in adenosine pre- and postconditioning group reduced significantly; but the level of SOD increased significantly. Histological examination and electron microscopy observations found in adenosine pre- and postconditioning group sinoatrial node injury also mitigated. These findings suggested that adenosine pre- or postconditioning were to reduce the incidence of ischemia/reperfusion arrhythmias, reduce myocardial ischemia reperfusion injury. The mechanism was to stabilize the SA node cells membrane and one possible mechanism involves modulation of HCN4 channels in pacemaker cells of the sinoatrial node.
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PMID:Protective effects of adenosine in rabbit sinoatrial node ischemia-reperfusion model in vivo: control of arrhythmia by hyperpolarization-activated cyclic nucleotide-gated (HCN)4 channels. 2084 41