Disease relevance of Kcnn4

• The effectiveness of blockade of the inwardly rectifying K+ current (IK1) in prevention of arrhythmias is unknown [1].
• RP58866, a selective IK1 blocker, is a potent and efficacious new antiarrhythmic drug in ischemia and reperfusion in rat, rabbit, and primate [1].
• CONCLUSIONS: The novel antiarrhythmic effects of tacrine, a drug with established blocking action on IK, IK1, and slow inward current, appear to result from QT widening in the rat (dependent partly on IK1 blockade in the ventricles and partly on drug induced sinus bradycardia) [2].
• In the present study, rats were treated with sodium selenite (5 micromol/kg body weight/day, ip) for 4 weeks and the parameters of contractile activity, action potential, L-type Ca2+-current (ICaL), as well as transient outward (Ito), inward rectifier (IK1), and steady state (Iss) K+-currents were investigated [3].
• Moreover, acidosis may differentially suppress I(to) and IK1, suggesting that these K+ channels exhibit dissimilar sensitivities to intracellular protons [4].

High impact information on Kcnn4

• Both astemizole and terfenadine suppressed the IK1 channel by 17% to 50% in a voltage-dependent manner in rat and guinea pig myocytes [5].
• Changes in voltage dependence of INa, inhibition of IK1, and membrane depolarization appear to contribute to the prolongation of the action potential, observed during phase I [6].
• Two-electrode voltage clamping was used to determine whole cell currents in Xenopus oocytes heterologously expressing rat CaSR and rat SK4 potassium channels [7].
• Voltage dependence of ATP-dependent K+ current in rat cardiac myocytes is affected by IK1 and IK(ACh) [8].
• The alpha 1-adrenergic agonist, methoxamine significantly reduced Ito and IK1 to the same extent in both sham and PMI cells, by about 35% and 20% respectively [9].

Chemical compound and disease context of Kcnn4

• OBJECTIVE: Tacrine was used as a tool to examine whether block of inward rectifying potassium current (IK1) represents a mechanism for suppression of arrhythmias induced by ischaemia and reperfusion [2].

Biological context of Kcnn4

• Consistent with these results, the magnitude (expressed in pA pF-1), voltage-dependence and kinetics of the inward rectifier (IK1), transient outward (Ito) and sustained (IK) K+ currents displayed little, if any dependence on age or gender [10].
• The decreasing rank order of potency was: transient outward K+ current (ITO, IC50 = 6.4 microM), a voltage dependent non-inactivating outward current (IK, IC = 11.5 microM), and the inward rectifier K+ current (IK1, IC50 = 46.9 microM) [11].
• No alterations in the magnitude and voltage dependence of inward rectifier (IK1) were found around the resting membrane potential [12].
• 5. In experiments without blocking NO and prostacyclin synthesis, the combined blockade of SK3 and IK1 reduced endothelium-dependent vasodilation [13].
• The respiratory burst was markedly inhibited by blockers of SK2 (apamin) and SK4 channels (clotrimazole and charybdotoxin), and to a lesser extent, by the potent Kv1.3 blocker agitoxin-2 [14].

Anatomical context of Kcnn4

• The aim of the present study was to examine concentration-dependent effects of terikalant, a blocker of inwardly rectifying K+ currents (IK1), rapidly activated delayed rectifying currents (IKr) and transient outward currents (Ito), on the contractility and effective refractory period in rat and guinea pig isolated papillary muscles [15].

Associations of Kcnn4 with chemical compounds

• Finally, in parallel with the reduction in SK4 message observed in animals deprived of dietary K+, carbachol-induced 86Rb+ secretion was abolished in dietary K+-depleted animals [16].
• Electrophysiological properties of tetraethylammonium (TEA) (10 mM)-insensitive, Ca2+ -dependent K+ currents in macropatches excised from RSA cells matched those of whole cell currents recorded from human embryonic kidney-293 cells heterologously expressing rat SK4/IK1 (rSK4/IK1) cloned from RSA cells [17].
• 3. Voltage-clamp recordings with the amphotericin-perforated patch method showed that H2O2 caused no significant changes in either the Ca(2+)-independent transient outward K+ current (Ito) or the inwardly rectifying K+ current (IK1) [18].
• The results of this study indicate that inhibition of Ito, Isus, and IK1 by tamoxifen may underlie AP prolongation in cardiac myocytes and thereby contribute to prolonged QT interval observed in patients [19].
• At concentrations greater than 5 microM, terikalant also altered the peak amplitudes of inward rectifier K+ currents (IK1) elicited with hyperpolarizing or depolarizing steps from holding potential and diminished IK1 resulting from voltage ramps [20].

Analytical, diagnostic and therapeutic context of Kcnn4

• Further investigations into the mechanism of antifibrillatory action of the specific IK1 blocker, RP58866, assessed using the rat dual coronary perfusion model [21].
• METHODS: The expression of IK channels was confirmed by PCR with specific primers for SK4 (IK) [22].
• Thus the inwardly rectifying potassium current (IK1) was measured in heart cells from rats of varying ages using patch-clamp techniques [23].

References