Potassium Channels in Cardiovascular System

Potassium channels of cardiac determine rate of heart and rest membrane also shape and period of movement. that's target for drug , toxic , neurotransmitter and hormones . potassium block the certain or more channels cause prolong action potential duration without slowing impulse rate .unfortunately , any drug will repolarization prolong QT of ECG . cardiac cell in mammalian , can divided to voltage gate and ligand gated channel .cardiac AP reflects between inside and outside to make balance. K + channels can be classified as voltage gateway channels (Kv) and linked channels. The first group contains fast and inactivated external components (Ito1), ultrasonic (IKur), fast (IKr) and slow (IKs) internal rectifier and delay rectifier (IK1), channels with internal correlation containing a decrease in the concentration of adenosine triphosphate.Activated by acetylcholine, K + channels have properties that are not fixed but have an effect on heart rate and vascular failure and enlargement of the heart and atrial fibrillation caused by arrhythmias. The brain population of the ventricular and atrial cells in stage zero is the result of activity in the Na and is repolarized in the first stage depends on the voltage and activation IKur, Ito1 in the second phase are balanced currents through Na + and Ca + channels and different rates of K + (iks, ikr, ikur ) The final stage leads to increased conductivity (IK1, IKs, IKr.)

Structure and function

Ito1 is quickly activated and stopped in response to depolarization. Ito2 Indicates the total current of K + depends on voltage, 4-aminopridine (4-AP), sensitive and disconnected from calcium (Ito1) and 4-AP insensitive, Cl2 or K + active-kali (Ito2). In atrial and ventricular muscle cells, Ito2 does not exist. Ito1 is responsible for rapid repolarization in the first stage and is determined when the plateau rises, these affect the activity of currents in the repolarization, especially ICaL and K + currents of late currents (IK). These differences affect the polarization of the heart associated with the differences in Ito1 strongly on Ca2 + and pass within cells when the entry of Ca2 + and the exchange of ICaL and Na + –Ca2 + is modified, and this leads to the development of Ca2 + weakness in the use of degrees in people with heart disease. The density of Ito1 is very high in Burkinje fibers, atrial tissue, epicardial and cardiac cells compared to endocardial cells. Point humerus, pectin muscle cells and ring area cells. The density of Ito1 is higher in the right than in the M cells of the left left ventricle and differences in the density of Ito1 across the ventricular wall correlate causally to the J wave of the ECG. The notable epitaxial ETO1contributes to the selective electrical retraction of the endothelium during ischemia and to the development of a marked dispersion of polarization between the normal and ischemic cardiac dipole, the vulva and the endocardium, ensuring a substrate for arrhythmia. Furthermore, cancellation caused by the dome of the flecaine in the potential dome of movement in endothelial cells but not in endocardial cells leads to a marked dispersion of repolarization across the ventricular wall leading, when accompanied by a prominent conduction delay connected to the Na + channel blockade.

>Pharmacology

Ito1 is blocked by 4-AP in the mM range in a way that indicates an interactive preference with the closed state. For many drugs on Ito1 produce 4-AP, quinidine and propafenone and their blockade is open to the channel and accelerate the inactivation of Ito produces quinidine, but flecainide, propafenone or tidesamil, its mass does not depend on the frequency of Ito1 and is produced by the slow rate of drug disintegration of the channel and reduces Ambasilide Ito1 by changing Connectivity instead of affecting gates. Ito1 blockers prolong APD in human atrial muscle cells and cerebral ventricular muscles. However, the effect of blocking Ito1 on repolarization may depend on other changes in currents. This reduces the density of Ito1 to shorten ventricular function. For Ito1 to increase the variation in APD and facilitate the initiation or persistence of arrhythmia then yield, the role of Ito1 in its control of cardiac polarization is unclear.

Regulation

Phosphorylation, mediated by protein kinase A (PKA) and C (PKC), changes the channel properties by modifying the kinetics or signaling of active channels on the cell surface. Phorbol 12-myristate 13-acetate (PMA), indeterminate activator of serine / threonine and tyrosine quinine proteins, suppresses both Kv4.2 and Kv4.3 and original Ito1 currents but not after pre-extinction with PKC inhibitors (chilarithrin) and staurosporine inhibitors Of the serine / threonine protein kinase. PKC supplies the time to disable and slows down the time to heal when ito1 is disabled. Alpha-adrenergic agonists (phenylephrine and methoxamine) reduce ITO-1 in murine ventricular muscle cells, while alpha-adrenergic agonists have no effect on ITO 1. In addition, phenylephrine and carbachol inhibit Kv4.3 streams only when they live, respectively, with The adreno-alpha receptors or the M1 receptors have also been inhibited by kelretrin, suggesting that PKC can be mediated by activation. In hKv4.1 channels, PMA causes a primitive increase followed by a decrease in amplitude and these effects are prevented by Storosporin or Killerethrin. Angiotensin 2 Ito1 inhibits rat ventricular muscle cells, an effect inhibited by PD123391, a selective antagonist of the AT2 receptor. This inhibition is canceled by Okadic acid, a phosphatase inhibitor 1 and 2a, which suggests that activation of the AT2 receptor activates the serine-threonine protein phosphatase to reduce the density of Ito1.

Pathological

Heart failure, myocardial ischemia and cardiac hypertrophy are associated with prolongation of APD, and this effect leads to disorganization of Itol1. Ito1 deficiency in heart failure may be adapted in the short term due to increased polarization during the cardiac cycle. It is known that there is a significant time of excitation and coupling or shrinkage, leading to lessening of the deficiency in cardiac output, and with long time it is unable to adapt because the prolongation APD may result in arrhythmia, either by two methods, one of which causes heterogeneous polarization or by increasing the probability of primitive or early polarization. Speculate that the higher organization of It o1 may be a protection mechanism that addresses excessive prolongation of APD and Ca2 + flow, in order to reduce the incidence of ventricular arrhythmias. Chronic AF reduces Ito1 intensity and KV4.3 mRNA levels. Hypothyroidism reduces signal for genes KCND2 (Kv4.2). Second type : The inward rectifier K+ current, structure and function : IK1 is a very strong K + rectifier in a limited period of membrane. The internal rectifier channels K + (Kir) control heart rate, regulate blood sugar level and release insulin. Kir channels are named because they work on more internal currents than membrane voltages V and EK equilibrium in the negative membrane, the conduction of KI1 is large compared to other currents, after which the comfortable membrane is attached to the EK. When depolarizing, the IK1 channels close quickly and are closed on all plateaus and open again when the negative potential is mv-20 and then IK1 enters the final phase of repolarization. Cardiac, low IK density in SA and AV where the diastole is less polarized in the atria and ventricles.

Pharmacology

Ba2 + is a strong blocker for IK1. Other inhibitors of IK1 such as: amiodarone, azimelide, clofilium, diltiazem, flecainide and flecainide KI blockers prolong the atrium, AV node and ventricular APD and are effective against various types of ventricular tachycardia. IK1 blockers. Produces polarization It is considered an effect that slows down the conduction speed because the Na + channels are not activated and they depend on the voltage and the QT goes on and all this arrhythmia. The heart rate increases the K + in the space between the narrow cells and this works to reduce APD and compensate IKr blockers to prolong APD.

Regulation

Isoproterenol and Forskolin inhibit IK1 in ventricular muscle cells, which suggests that IK1 is prevented by phosphorus PKA. Isoprotrinol is inhibited by acetylcholine and propranolol. PMA is converted into the atrial muscle and in the kir2.1b channels by IK1. This effect inhibits and mutations of PKC phosphorylation sites (S64A, T353A). In the atrial, methoxamine IK is inhibited by H-9, a specific PKC inhibitor, and suggests that α1 adrenergic stimulation reduces IK1 through PKC-based methods and passively controls Kir2.1 channels by a tyrosine-based phosphorylation process. Acid modifies IK1 Its effect depends on several types, PIP2 activates directly IK1, by electrostatic reaction of groups with negative charges of PIP2 - and C-terminal has charged residues - Kir channel

Pathology

IK1 is regulated with automatic high pressure, in examples of cardiac hypertrophy and in patients with severe heart failure and myocardial failure. Ventricular density decreases homogeneously IK1 via insufficiency in heart failure. It was observed that IK1 density decreased in Purkinje cells after myocardial infarction, but this decrease is greater in epicardial than myocardial cells. Ventricular muscle cells decreased in patients with longer APD and membrane potential less comfortable than those of patients with cardiomyopathy. Reduced regulation of IK1 results in membrane polarization and prolongation of APD, both after early polarization delay and IK1 increases its density in patients with chronic AF.These mutations Kir2.1 KCNJ2 indicate the occurrence of negative effects controlling the current and has been linked to Andersen syndrome, this is a genetic disease is the most important thing characterized by periodic paralysis and dysfunction in the formation and when prolonging the QT and ventricular heartbeat is irregular.

In conclusion

However there is an unclear understanding of potassium currents in the heart and how there is a dysfunction of their heartbeat functions. The locations of potassium channels in the heart make the treatment more selective. All types of potassium channels depend on a particular voltage and each one has a specific role in repolarization and polarization varies depending on the characteristics and types of heart.