Ca current facilitation during postrest recovery depends on Ca entry

L. V. Hryshko, Donald M Bers

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Abstract

Whole cell Ca current (I(Ca)) recovery after periods of rest was examined in voltage-clamped rabbit ventricular myocytes with Na and K currents suppressed. To evaluate rest-dependent changes in I(Ca) independent of the effects of sarcoplasmic reticular (SR) Ca release, the intracellular Ca ([Ca](i)) transients were usually buffered by ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (10 mM) in the patch pipette. When voltage-clamp pulses were resumed (at 0.5 Hz) after a period of rest, several pulses were required to reattain steady-state peak I(Ca) levels. From depolarized holding potentials between -40 and -50 mV, peak I(Ca) of the first pulse was large and gradually decayed to steady-state levels (negative I(Ca) staircase). This potentiation of postrest I(Ca) was mediated by increased recovery from inactivation of Ca channels during the rest period. In contrast, with more negative holding potentials (-70 to -90 mV), the initial postrest I(Ca) was relatively small (rest depression) and facilitation of I(Ca) was then observed for subsequent pulses (positive I(Ca) staircase). This I(Ca) facilitation was mediated by a progressive decrease in the I(Ca) inactivation rate. Depression of the initial postrest I(Ca) required 10-15 s of rest to fully develop and became relatively constant for longer rest intervals (30-300 s). Postrest I(Ca) depression (i.e., subsequent I(Ca) facilitation) was abolished by replacement of extracellular Ca ([Ca](o)) with either Ba or Sr. Thus I(Ca) facilitation depends on Ca entry. Increasing [Ca](o) increased postrest I(Ca) facilitation and reducing [Ca](o) had an opposite effect. When I(Ca) was altered by changing step potential, maximal I(Ca) facilitation occurred when I(Ca) was maximal. Thus I(Ca) facilitation can be graded by the amount of Ca entry. As I(Ca) facilitation was not altered by ryanodine, this response is not likely to be due to SR Ca release. However, increasing [Ca](i) buffering by using 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in the pipette abolished the I(Ca) staircase. Our results indicate that Ca entry can facilitate subsequent I(Ca), presumably through actions occurring near the sarcolemma. These local changes in [Ca](i) lead to a progressive slowing in the rate of I(Ca) inactivation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume259
Issue number3 28-3
StatePublished - 1990

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Keywords

  • calcium current facilitation
  • calcium current inactivation
  • rest recovery

ASJC Scopus subject areas

  • Physiology

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