Excitation–contraction coupling in human heart failure examined by action potential clamp in rat cardiac myocytes

Modulation of ventricular transient outward K+ current by acidosis and its effects on excitation-contraction coupling

“…11), is consistent with canine myocyte simulations (21) and rat myocyte experiments (11,43,44) and is likely mediated by the reduced voltage driving force acting on Ca 2ϩ current. Epi myocytes displayed the greatest change in peak I Ca,L , reflecting their higher I to density and thus more pronounced slowing of phase 1.…”

“…These effects appear to be mediated, in part, by pH i -induced changes in I to and are more prominent in Epi than PM myocytes. Several earlier studies reported that changes in phase 1 repolarization significantly affect I Ca,L and CaTs during APs (6,11,43,44). However, to our knowledge, this is the first demonstration that changes in ventricular repolarization induced by low pH i have significant indirect effects on calcium handling.…”

“…By modulating the initial voltage trajectory of the AP, I to importantly influences the overall AP waveform through voltage-dependent effects on other ionic currents such as L-type calcium current (I Ca,L ), Na ϩ /Ca 2ϩ exchange (NCX) current, and delayed rectifier currents (34). In this regard, several studies have shown that inhibition of I to markedly affects excitation-contraction (E-C) coupling by altering transsarcolemmal Ca 2ϩ flux via I Ca,L and NCX, with secondary effects on calcium loading of the sarcoplasmic reticulum (SR) (5,6,11,13,27,42,43,53).The expression and magnitude of cardiac I to are regulated by a variety of factors and conditions including hormones, metabolic inhibition, and hypertrophy/failure with consequent effects on AP configuration (32, 36). In addition, previous work has shown that I to in rat ventricular myocytes, measured at room temperature, is altered by extracellular acidosis [low extracellular pH (pH o )] (50), intracellular acidosis [low intracellular pH (pH i )] (58, 59), and simultaneous reductions in pH o and pH i (combined acidosis) (24).…”

“…By modulating the initial voltage trajectory of the AP, I to importantly influences the overall AP waveform through voltage-dependent effects on other ionic currents such as L-type calcium current (I Ca,L ), Na ϩ /Ca 2ϩ exchange (NCX) current, and delayed rectifier currents (34). In this regard, several studies have shown that inhibition of I to markedly affects excitation-contraction (E-C) coupling by altering transsarcolemmal Ca 2ϩ flux via I Ca,L and NCX, with secondary effects on calcium loading of the sarcoplasmic reticulum (SR) (5,6,11,13,27,42,43,53).…”

Advances in patch clamp technique: towards higher quality and quantity

“…Cooper et al (2010) found that Ca 2+ release from the sarcoplasmic reticulum is significantly decreased when the cell is stimulated with AP waveform characteristic for the cardiac failure (an absence of AP notch). This behaviour indicates an impaired excitation-contraction coupling.…”