title: On the source of Ca(2+) activating the tonic component of contraction of myocytes of guinea pig heart.
abstract: OBJECTIVE
  Contractions of isolated, single myocytes of guinea pig heart stimulated at 37 degrees C consist of a phasic component and a voltage dependent tonic component. In this study we investigated the source of Ca(2+) activating the tonic component.
  
  
  METHODS
  Experiments were performed at 37 degrees C in ventricular myocytes of guinea pig heart. Voltage-clamped cells were stimulated by the pulses from the holding potential of -40 to +5 mV. [Ca(2+)](i) was monitored as fluorescence of Indo 1-AM and contractions were recorded with the TV edge-tracking system.
  
  
  RESULTS
  Superfusion of 5 mmol/l Ni(2+) during 30 s pause did not inhibit subsequent biphasic Ca(2+) transients and contractions despite inhibition of Ca(2+) current and Na(+)/Ca(2+) exchange. KB-R7943 (5 micromol/l) or intracellular dialysis with 0 Na(+) solution, both of which inhibit reversed Na(+)/Ca(2+) exchange, decreased amplitude of Ca(2+) transients and contractions by approximately 40%. The ratio of amplitudes of tonic to phasic component was increased by Ni(2+) and was not changed by KB-R7943 or 0 Na(+)(i). Ryanodine (200 micromol/l) inhibited both components of contractions in cells superfused with Ni(2+). The phasic component but not the tonic component was inhibited by 20 micromol/l nifedipine in cells superfused with Ni(2+).
  
  
  CONCLUSIONS
  Tonic component of contraction of single myocytes of guinea pig heart is not activated by Ca(2+) current or by the reverse mode Na(+)/Ca(2+) exchange as currently proposed in literature. Rather, it is activated by Ca(2+) released from the sarcoplasmic reticulum. However, kinetics and mechanism of release seem to be quite different from those of Ca(2+) fraction activating the phasic component of contraction.
authors.affiliation: Department of Clinical Physiology, Medical Centre of Postgraduate Education, Marymoncka 99, 01-813, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Emanuel
authors.forename: U
authors.initials: U
authors.lastname: Mackiewicz
authors.forename: B
authors.initials: B
authors.lastname: Lewartowski
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008856:Microscopy, Fluorescence; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010477:Perfusion; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002121:Calcium Channel Blockers; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D009532:Nickel; D012964:Sodium; D013890:Thiourea; D002118:Calcium