Inward current related to contraction in guinea-pig ventricular myocytes.
1. A component of inward current has been identified in isolated guinea-pig ventricular cells that is closely correlated with the contraction of the cell and not with the rapidly activated calcium current. This is a delayed current most clearly seen as a current 'tail' after 50-200 ms depolarizing pulses. At 22 degrees C the delayed current has a maximum amplitude of approximately 0.5 nA at -40 mV (consistently 10-20% of the peak amplitude of the calcium current) and decays with a half time of approximately 150 ms. 2. Paired-pulse protocols show that at pulse intervals (300-400 ms) at which the calcium current is nearly fully reprimed, the delayed component is very small. It recovers over a time course of several seconds, as does the contraction. Adrenaline speeds the decay of the delayed current (approximately 50%) and similarly accelerates cell relaxation. Adrenaline also shortens the recovery time of both the contraction and the delayed current. 3. During long trains of repetitive pulses, the delayed current amplitude follows that of the contraction 'staircase'. The half-time of the decay of the current 'tail' also matches that of contraction and suggests that both may reflect the time course of the underlying intracellular calcium transient. 4. The half-time of decay of the delayed current is only moderately voltage dependent over the potential range -80 to 0 mV. The amplitude of the delayed current normally reaches a minimum around -20 mV and increases at more negative potentials. 5. The voltage dependence and kinetics of decay of the current show that it should flow and decay largely during the action potential plateau and repolarization rather than during diastole. 6. Diffusion of high concentrations of EGTA into cells abolishes the delayed current and cell contraction. Under these conditions the fast calcium current is increased and its inactivation delayed. 7. When calcium is replaced by strontium, the delayed current amplitude is greatly reduced even though the contraction is larger and slower. 8. The results are consistent with the hypothesis that the delayed inward current is activated by the intracellular calcium transient. It may be carried by the sodium-calcium exchange process and/or by calcium-activated non-specific channels (especially when interal calcium is elevated by reduction of external sodium). 9. In the presence of 1 microM-ryanodine, the calcium current is greatly reduced, whereas the delayed current is not significantly altered.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013324:Strontium / Q000494:pharmacology; D013997:Time Factors
D007473:Ion Channels; D012433:Ryanodine; D004533:Egtazic Acid; D012964:Sodium; D002118:Calcium; D004837:Epinephrine; D013324:Strontium