title: Activation of purinergic receptors triggers oscillatory contractions in adult rat ventricular myocytes.
abstract: Extracellular ATP is an important neurotransmitter that modulates cardiac function by activation of purinergic receptors. In this study, the effect of P2 purinergic receptor activation on contractions and on [Ca2+]i was investigated in adult rat ventricular myocytes. Fura 2 was used to measure [Ca2+]i, and video edge detection was used to measure contraction. Superfusion of 2-methylthio-adenosine-5'-triphosphate (2-M-S-ATP) over quiescent myocytes induced oscillations in contraction and in [Ca2+]i. The frequency of the oscillatory contractions increased with increasing concentrations of 2-M-S-ATP, but the amplitude of contractions varied from cell to cell and was independent of the concentration of 2-M-S-ATP. During electrical stimulation, activation of purinergic receptors in myocytes potentiated the amplitude of contraction and induced arrhythmias. In populations of quiescent myocytes, the plateau phase of the [Ca2+]i signal evoked by 2-M-S-ATP could be shown to represent summed oscillations in [Ca2+]i in individual cells. Pretreatment of quiescent myocytes with thapsigargin or caffeine reduced or abolished the oscillations in contractions and in [Ca2+]i triggered by 2-M-S-ATP, indicating a dependence of the oscillations on uptake and release of Ca2+ by the sarcoplasmic reticulum. These data demonstrate the novel phenomenon that activation of purinergic receptors in quiescent myocytes stimulates oscillations in [Ca2+]i and contraction. In electrically stimulated myocytes, activation of purinergic receptors triggers oscillatory contractions and potentiates the amplitude of electrically triggered contractions.
authors.affiliation: Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: B X
authors.initials: BX
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.forename: B K
authors.initials: BK
authors.lastname: McConnell
authors.forename: D S
authors.initials: DS
authors.lastname: Damron
authors.forename: M
authors.initials: M
authors.lastname: Bond
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009991:Oscillometry; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D016276:Ventricular Function
chemical_list: D011983:Receptors, Purinergic; D013873:Thionucleotides; D002110:Caffeine; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium; C008501:2-methylthio-ATP