Abstract: | The lipid bilayertechnique was used to characterize theCa2+ dependence of a fastK+ channel formed by a synthetic17-amino acid segment OaCNP-39-(1-17)] ofa 39-amino acid C-type natriuretic peptide (OaCNP-39) found in platypus (Ornithorhynchusanatinus) venom (OaV). TheOaCNP-39-(1-17)-formed K+ channel was reversiblydependent on1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-buffered cis (cytoplasmic)Ca2+ concentration(Ca2+]cis).The channel was fully active whenCa2+]ciswas >104 M andtrans (luminal)Ca2+ concentration was 1.0 mM, butnot at lowCa2+]cis.The open probability of single channels increased from zero at1 × 106 McisCa2+ to 0.73 ± 0.17 (n = 22) at103 McisCa2+. Channel openings to themaximum conductance of 38 pS were rapidly and reversibly activated whenCa2+]cis,but not transCa2+ concentration(n = 5), was increased to >5 × 104 M(n = 14). Channel openings to thesubmaximal conductance of 10.5 pS were dominant at5 × 104 MCa2+.K+ channels did not open whencisMg2+ orSr2+ concentrations were increasedfrom zero to 103 M or whenCa2+]ciswas maintained at 106 M(n = 3 and 2). The Hill coefficientand the inhibition constant were 1 and 0.8 × 104 McisCa2+, respectively. Thisdependence of the channel on highCa2+]cissuggests that it may become active under1) physiological conditions whereCa2+ levels are high, e.g., duringcardiac and skeletal muscle contractions, and2) pathological conditions that leadto a Ca2+ overload, e.g., ischemicheart and muscle fatigue. The channel could modify a cascade ofphysiological functions that are dependent on theCa2+-activatedK+ channels, e.g., vasodilationand salt secretion. |