Sarcoplasmic reticulum Ca2+ content, L-type Ca2+ current and the Ca2+ transient in rat myocytes during beta-adrenergic stimulation

J Physiol. 1997 Dec 1;505 ( Pt 2)(Pt 2):385-402. doi: 10.1111/j.1469-7793.1997.385bb.x.


1. The effect of beta-adrenergic stimulation on the relationship between the intracellular Ca2+ transient and the amplitude of the L-type Ca2+ current (ICa) has been investigated in ventricular myocytes isolated from rat hearts. Intracellular [Ca2+] was monitored using fura-2 during field stimulation and while membrane potential was controlled using voltage clamp techniques. 2. The increase in the amplitude, and the rate of decline, of the Ca2+ transient produced by isoprenaline (1.0 mumol l-1) was not significantly different in myocytes generating action potentials and in those voltage clamped with pulses of constant duration and amplitude. 3. Under control conditions, the current-voltage (I-V) relationship for ICa was bell shaped. The amplitude of the Ca2+ transient also showed a bell-shaped voltage dependence. In the presence of isoprenaline, the amplitude of both ICa and the Ca2+ transient was greater at all test potentials and the I-V relationship maintained its bell-shaped voltage dependence. However, the size of the Ca2+ transient was no longer graded with changes in the amplitude of ICa: a small ICa could now elicit a maximal Ca2+ transient. 4. Rapid application of caffeine (10 mmol l-1) was used to elicit Ca2+ release from the sarcoplasmic reticulum (SR). Isoprenaline increased the integral of the subsequent rise in cytoplasmic [Ca2+] to 175 +/- 13% of control. 5. Abbreviation of conditioning pulse duration in the presence of isoprenaline was used to reduce the amplitude of the Ca2+ transient to control levels. Under these conditions, the amplitude of the Ca2+ transient was again graded with the amplitude of ICa in the same way as under control conditions. 6. Nifedipine (2 mumol l-1) was also used to decrease Ca2+ transient amplitude in the presence of isoprenaline. In the presence of isoprenaline and nifedipine, the amplitude of the Ca2+ transient again showed a bell-shaped voltage dependence. 7. The SR Ca(2+)-ATPase inhibitor thapsigargin (2.5 mumol l-1) reduced the effect of isoprenaline on the amplitude of the Ca2+ transient. In the presence of thapsigargin, the size of the Ca2+ transient increased as ICa increased in response to isoprenaline. 8. These data suggest that the increase in the amplitude of the Ca2+ transient produced by beta-adrenergic stimulation in cardiac muscle is due to an increase in the gain of the SR Ca2+ release process, due principally to an increase in the Ca2+ content of the SR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / physiology*
  • Calcium Channels, L-Type
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Cells, Cultured
  • Heart / drug effects
  • Heart / physiology*
  • Isoproterenol / pharmacology*
  • Kinetics
  • Male
  • Membrane Potentials
  • Myocardium / metabolism*
  • Nifedipine / pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta / physiology
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism*
  • Thapsigargin / pharmacology


  • Adrenergic beta-Agonists
  • Calcium Channels
  • Calcium Channels, L-Type
  • Receptors, Adrenergic, beta
  • Caffeine
  • Thapsigargin
  • Calcium-Transporting ATPases
  • Nifedipine
  • Isoproterenol
  • Calcium