title: Mechanism of activation of the tonic component of contraction in myocytes of guinea pig heart.
abstract: OBJECTIVE
  Contractions of myocytes of guinea pig heart consist of a phasic component relaxing independently on the voltage and a tonic component relaxing upon repolarization. We found previously that Ca(2+) activating the tonic component is released from the sarcoplasmic reticulum. In this study, we analysed the mechanism of activation and maintenance of this release.
  
  
  METHODS
  Experiments were performed at 37 degrees C in ventricular myocytes of guinea pig heart. Voltage-clamped myocytes were stimulated by the pulses of the duration of 300 ms to 15-45 s from the holding potential of -40 to +5 mV. [Ca(2+)](i) was monitored as fluorescence of Indo-1 and contractions were recorded with the TV edge-tracking system.
  
  
  RESULTS
  Myocytes responded to the short and long pulses with phasic contraction or Ca(2+) transient followed by the sustained contraction or increase in [Ca(2+)](i). Repolarization brought about relaxation. 10 mmol L(-1) Ni(2+) blocking Na(+)/Ca(2+) exchange superfused during the tonic component increased its amplitude. Superfusion of Ca(2+)-free solution during sustained contraction brought about relaxation both in normal cells and in cells superfused with Ni(2+) despite preserved sarcoplasmic reticulum Ca(2+) content assessed with caffeine spritz. Relaxing effect of Ca(2+)-free solution was not affected by carboxyeosin, a blocker of sarcolemmal Ca(2+)-ATPase. Tonic component of contraction and of Ca(2+) transient was inhibited by 200 micromol L(-1) ryanodine, a blocker of Ca(2+) release channels of the sarcoplasmic reticulum and by 20 micromol L(-1) nifedipine, a blocker of L-type I(Ca).
  
  
  CONCLUSIONS
  Tonic component of contraction results from Ca(2+) release via the sarcoplasmic reticulum Ca(2+) channels activated by sustained, nifedipine-sensitive and Ni(2+)-insensitive Ca(2+) influx. Alternatively, the SR Ca(2+) release is activated by voltage, the dihydropyridine receptors acting like voltage sensors.
authors.affiliation: Department of Clinical Physiology, Medical Center of Postgraduate Education, Marymoncka, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Mackiewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Emanuel
authors.forename: Bohdan
authors.initials: B
authors.lastname: Lewartowski
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D006168:Guinea Pigs; D007552:Isotonic Solutions / Q000494:pharmacology; D032342:Muscle Cells / Q000166:cytology* / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000037:antagonists & inhibitors; D018408:Patch-Clamp Techniques; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D007552:Isotonic Solutions; C037692:Tyrode's solution; D012433:Ryanodine; D009532:Nickel; D000242:Cyclic AMP; D009543:Nifedipine; D002118:Calcium