%0 Journal Article %1 Petr_2003_801 %A Petroff, Mart�n G Vila %A Palomeque, Julieta %A Mattiazzi, Alicia R %D 2003 %J J. Physiol. %K 12938675 ATPase, Agents, Animals, Calcium Calcium, Calcium-Binding Cardiac, Cardiotonic Cats, Cells, Conduction Contraction, Cultured, Cytosol, Dyes, Electric Exchanger, Fluorescent Gov't, Heart Heart, In Indoles, Muscle Muscles, Myocardial Myocytes, Non-U.S. Ouabain, Papillary Phosphorylation, Proteins, Rate, Rats, Relaxation, Research Signaling, Sodium, Sodium-Calcium Stimulation, Support, System, Thiourea, Vitro, {C}a$^{2+}$-Transporting %N Pt 3 %P 801--817 %R 10.1113/jphysiol.2003.044321 %T Na$^+$-Ca$^2+$ exchange function underlying contraction frequency inotropy in the cat myocardium. %U http://dx.doi.org/10.1113/jphysiol.2003.044321 %V 550 %X In most mammalian species, an increase in stimulation frequency (ISF) produces an increase in contractility (treppe phenomenon), which results from larger Ca$^2+$ transients at higher frequencies, due to an increase in sarcoplasmic reticulum Ca$^2+$ load and release. The present study attempts to elucidate the contribution of the Na$^+$-Ca$^2+$ exchanger (NCX) to this phenomenon. Isolated cat ventricular myocytes, loaded with Ca$^2+$i- and Na$^+$i-sensitive probes, were used to determine whether the contribution of the NCX to the positive inotropic effect of ISF is due to an increase in Ca$^2+$ influx (reverse mode) and/or a decrease in Ca$^2+$ efflux (forward mode) via the NCX, due to frequency-induced Na$^+$i elevation, or whether it was due to the reduced time for the NCX to extrude Ca$^2+$. The results showed that the positive intropic effect produced by ISF was temporally dissociated from the increase in Na$^+$i and was not modified by KB-R7943 (1 or 5 microM), a specific blocker of the reverse mode of the NCX. Whereas the ISF from 10 to 30 beats min(-1) (bpm) did not affect the forward mode of the NCX (assessed by the time to half-relaxation of the caffeine-induced Ca$^2+$ transient), the ISF to 50 bpm produced a significant reduction of the activity of the forward mode of the NCX, which occurred in association with an increase in Na$^+$i (from 4.33+/-0.40 to 7.25+/-0.50 mM). However, both changes became significant well after the maximal positive inotropic effect had been reached. In contrast, the positive inotropic effect produced by ISF from 10 to 50 bpm was associated with an increase in diastolic Ca$^2+$i, which occurred in spite of a significant increase in the relaxation rate and at a time at which no increases in Na$^+$i were detected. The contribution of the NCX to stimulus frequency inotropy would therefore depend on a decrease in NCX-mediated Ca$^2+$ efflux due to the reduced diastolic interval between beats and not on Na$^+$i-dependent mechanisms.

@article{Petr_2003_801, abstract = {In most mammalian species, an increase in stimulation frequency ({ISF}) produces an increase in contractility (treppe phenomenon), which results from larger {C}a$^{2+}$ transients at higher frequencies, due to an increase in sarcoplasmic reticulum {C}a$^{2+}$ load and release. The present study attempts to elucidate the contribution of the {N}a$^{+}$-{C}a$^{2+}$ exchanger (NCX) to this phenomenon. Isolated cat ventricular myocytes, loaded with [{C}a$^{2+}$]i- and [{N}a$^{+}$]i-sensitive probes, were used to determine whether the contribution of the NCX to the positive inotropic effect of {ISF} is due to an increase in {C}a$^{2+}$ influx (reverse mode) and/or a decrease in {C}a$^{2+}$ efflux (forward mode) via the NCX, due to frequency-induced [{N}a$^{+}$]i elevation, or whether it was due to the reduced time for the NCX to extrude {C}a$^{2+}$. The results showed that the positive intropic effect produced by {ISF} was temporally dissociated from the increase in [{N}a$^{+}$]i and was not modified by {KB}-R7943 (1 or 5 microM), a specific blocker of the reverse mode of the NCX. Whereas the {ISF} from 10 to 30 beats min(-1) (bpm) did not affect the forward mode of the NCX (assessed by the time to half-relaxation of the caffeine-induced {C}a$^{2+}$ transient), the {ISF} to 50 bpm produced a significant reduction of the activity of the forward mode of the NCX, which occurred in association with an increase in [{N}a$^{+}$]i (from 4.33+/-0.40 to 7.25+/-0.50 mM). However, both changes became significant well after the maximal positive inotropic effect had been reached. In contrast, the positive inotropic effect produced by {ISF} from 10 to 50 bpm was associated with an increase in diastolic [{C}a$^{2+}$]i, which occurred in spite of a significant increase in the relaxation rate and at a time at which no increases in [{N}a$^{+}$]i were detected. The contribution of the NCX to stimulus frequency inotropy would therefore depend on a decrease in NCX-mediated {C}a$^{2+}$ efflux due to the reduced diastolic interval between beats and not on [{N}a$^{+}$]i-dependent mechanisms.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Petroff, Mart�n G Vila and Palomeque, Julieta and Mattiazzi, Alicia R}, biburl = {https://www.bibsonomy.org/bibtex/2e277d54e52eaa963e35b2e682ff54850/hake}, description = {The whole bibliography file I use.}, doi = {10.1113/jphysiol.2003.044321}, file = {Petr_2003_801.pdf:Petr_2003_801.pdf:PDF}, interhash = {4eb95cb6943635c5c6721fea148d7f6c}, intrahash = {e277d54e52eaa963e35b2e682ff54850}, journal = {J. Physiol.}, keywords = {12938675 ATPase, Agents, Animals, Calcium Calcium, Calcium-Binding Cardiac, Cardiotonic Cats, Cells, Conduction Contraction, Cultured, Cytosol, Dyes, Electric Exchanger, Fluorescent Gov't, Heart Heart, In Indoles, Muscle Muscles, Myocardial Myocytes, Non-U.S. Ouabain, Papillary Phosphorylation, Proteins, Rate, Rats, Relaxation, Research Signaling, Sodium, Sodium-Calcium Stimulation, Support, System, Thiourea, Vitro, {C}a$^{2+}$-Transporting}, month = Aug, number = {Pt 3}, pages = {801--817}, pii = {jphysiol.2003.044321}, pmid = {12938675}, timestamp = {2009-06-03T11:21:25.000+0200}, title = {{N}a$^{+}$-{C}a$^{2+}$ exchange function underlying contraction frequency inotropy in the cat myocardium.}, url = {http://dx.doi.org/10.1113/jphysiol.2003.044321}, volume = 550, year = 2003 }