The effect of tetracaine on spontaneous Ca2+ release and sarcoplasmic reticulum calcium content in rat ventricular myocytes.
1. The effects of tetracaine were studied on voltage-clamped rat ventricular myocytes, which exhibited Ca2+ overload as identified by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) as shown by the associated contractions. This Ca2+ release was initially abolished by tetracaine before returning at a lower frequency, but greater amplitude, than the control. On removal of tetracaine, there was a burst of spontaneous Ca2+ release activity. All these effects were dose dependent, from 25 to 200 microM tetracaine. 2. The spontaneous Ca2+ release activated an inward Na(+)-Ca2+ exchange current as Ca2+ was pumped out of the cell. The integral of this current (i.e. the Ca2+ efflux) was increased in the presence of tetracaine. The calcium efflux per unit time was unaffected by tetracaine. 3. The SR Ca2+ content was increased by tetracaine, as shown by the integral of the caffeine-evoked Na(+)-Ca2+ exchange current. The increase of SR Ca2+ content was equal to the extra Ca2+ lost from the cell during the burst on removal of tetracaine, and to estimates of the extra calcium gained over the quiescent period following addition of tetracaine. 4. It is concluded that partial inhibition of calcium-induced calcium release increases SR Ca2+ content. In the steady state, cell Ca2+ balance is maintained as the lower frequency of spontaneous release (that activates efflux) is compensated for by their greater size.
Overend
C L
CL
Department of Veterinary Preclinical Sciences, University of Liverpool, UK.
Eisner
D A
DA
O'Neill
S C
SC
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size / Q000502:physiology; D004594:Electrophysiology; D006352:Heart Ventricles / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism*; D013748:Tetracaine / Q000494:pharmacology*
D000779:Anesthetics, Local; D010726:Phosphodiesterase Inhibitors; D013748:Tetracaine; D002110:Caffeine; D002118:Calcium