Four different components contribute to outward current in rat ventricular myocytes

Abstract

In rat ventricle, two Ca2+-insensitive components of K+ current have been distinguished kinetically and pharmacologically, the transient, 4-aminopyridine (4-AP)-sensitive I to and the sustained, tetraethylammonium (TEA)-sensitive I K. However, a much greater diversity of depolarization-activated K+ channels has been reported on the level of mRNA and protein. In the search for electrophysiological evidence of further current components, the whole cell voltage-clamp technique was used to analyze steady-state inactivation of outward currents by conditioning potentials in a wide voltage range. Peak ( I peak) and late ( I late) currents during the test pulse were analyzed by Boltzmann curve fitting, producing three fractions each. Fractions a and b had different potentials of half-maximum inactivation ( V 0.5); the third residual fraction, r, did not inactivate. Fractions a for I peak and I late had similar relative amplitudes and V 0.5 values, whereas size and V 0.5 of fractions b differed significantly between I peak and I late. Only b of I peak was transient, suggesting a relation with I to, whereas a, b, and r of I late appeared to be three different sustained currents. Therefore, four individual outward current components were distinguished: I to( b of I peak), I K( a), the steady-state current I ss( r), and the novel current I Kx( b of I late). This was further supported by differential sensitivity to TEA, 4-AP, clofilium, quinidine, dendrotoxin, heteropodatoxin, and hanatoxin. With the exception of I to, none of the currents exhibited a marked transmural gradient. Availability of I K was low at resting potential; nevertheless, I K contributed to action potential shortening in hyperpolarized subendocardial myocytes. In conclusion, on the basis of electrophysiological and pharmacological evidence, at least four components contribute to outward current in rat ventricular myocytes.

Inhibition of Kv2.1 Voltage-dependent K+Channels in Pancreatic β-Cells Enhances Glucose-dependent Insulin Secretion

“…Therefore, acute inhibition of Kv2.1 would provide valuable new information. We have now extended our previous studies using a novel non-peptide compound (the bispidine derivative, C-1) related to class III antiarrhythmic agents such as tedisamil (35) that block delayed-rectifier K ϩ channels in the heart (36), of which Kv2.1 is a major component (37).…”

Role of PKC in autocrine regulation of rat ventricular K+currents by angiotensin and endothelin

“…Earlier work by Himmel et al (21) provided a comprehensive analysis of the different current components by analyzing the inactivation characteristics of total outward currents in rat ventricular cells. They showed that a protocol consisting of 2,000-ms prepulses to potentials ranging from Ϫ140 to ϩ20 mV (in 10-mV steps except for the range of Ϫ60 and Ϫ20 mV, in which 5-mV steps were used), followed by test pulses to ϩ60 mV, allowed the measurement of steady-state inactivation of currents that could best be fit by two Boltzmann functions.…”

“…The channel proteins encoded by Kv4.2 and Kv4.3 underlie the transient outward current in rat ventricular cells (14,34). The sustained current has several components (21) and is the complex expression of several channel proteins (34). In our experiments, antibodies directed against Kv4.2, Kv1.2 (Alomone), and Kv4.3 (Alomone and an antibody kindly provided by Dr. J. Nerbonne) were used.…”

Genetic manipulation of calcium-handling proteins in cardiac myocytes. II. Mathematical modeling studies

“…To make the model rat specific, the voltage-activated K ϩ channel representation of Winslow et al was replaced by a formulation representative of rat cardiac myocytes (16). This novel representation, as well as other minor changes on other currents, is discussed in detail in Tables 1-6.…”