Sarcoplasmic reticulum Ca2+ content, L‐type Ca2+ current and the Ca2+ transient in rat myocytes during β‐adrenergic Stimulation

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Abstract
The effect of β‐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. The increase in the amplitude, and the rate of decline, of the Ca2+ transient produced by isoprenaline (1.0 μmol l−1) was not significantly different in myocytes generating action potentials and in those voltage clamped with pulses of constant duration and amplitude. 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. 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. 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. Nifedipine (2 μmol 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. The SR Ca2+ ‐ATPase inhibitor thapsigargin (2.5 μmol 1−1) 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. These data suggest that the increase in the amplitude of the Ca2+ transient produced by β‐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.

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