Cellular origins of the transient inward current in cardiac myocytes. Role of fluctuations and waves of elevated intracellular calcium

J. R. Berlin, M. B. Cannell, W. J. Lederer

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Activation of the transient inward current (I(TI)) by a rise in intracellular calcium concentration ([Ca2+](i)) is believed to be responsible for generating triggered cardiac arrhythmias. In this study, the cellular basis of the rise in [Ca2+](i) that activates I(TI) and aftercontractions in single rat venticular myocytes was examined. [Ca2+](i) was measured both indirectly by cell contraction and directly with fura-2. Under conditions that caused steady-state [Ca2+](i) to increase (i.e., calcium overload) membrane repolarization after a voltage-clamp depolarization resulted in the appearance of I(TI) that was similar in many respects to that observed in multicellular preparations. This I(TI) occurred at the same time that [Ca2+](i) spontaneously increased and preceded the aftercontraction by 60-90 msec. However, I(TI) recorded from a single cells was variable in time course and amplitude (unlike that observed in multicellular preparations). Examination of cell contraction and digital imaging of fura-2 fluorescence showed that I(TI) was often associated with propagating regions of increased [Ca2+(i), which arose from discrete sites of origin within the cell. Apparently synchronous aftercontractions could also be associated with multiple propagating waves of [Ca2+](i). The variation in the time course and amplitude of I(TI) in single cells appeared to be due to changes in the location and number of sites of origin for the waves of [Ca2+](i). After the fist aftercontraction and I(TI), desynchronization of the sites of origin of increased [Ca2+](i) occurred, and this resulted in a decrease in the amplitude of I(TI) and an increase in its duration. We conclude that the variability seen in single cells arises from changes in the pattern of spontaneous Ca2+ release. Such phenomena will seriously complicate interpretation of multicellular data, even when [Ca2+](i) is measured directly.

Original languageEnglish (US)
Pages (from-to)115-126
Number of pages12
JournalCirculation research
Issue number1
StatePublished - 1989
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine


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