%0 Journal Article %1 Alta_2007_563 %A Altamirano, Julio %A Bers, Donald M %D 2007 %J Am J Physiol Heart Circ Physiol %K Action Animals; Calcium Calcium, Cardiac, Cells, Channel Channels, Contraction, Cultured; Gating, Ion L-Type, Myocardial Myocytes, Potentials, Rabbits metabolism; physiology; %N 1 %P H563--H573 %R 10.1152/ajpheart.00469.2006 %T Effect of intracellular Ca2+ and action potential duration on L-type Ca2+ channel inactivation and recovery from inactivation in rabbit cardiac myocytes. %U http://dx.doi.org/10.1152/ajpheart.00469.2006 %V 293 %X Ca(2+) current (I(Ca)) recovery from inactivation is necessary for normal cardiac excitation-contraction coupling. In normal hearts, increased stimulation frequency increases force, but in heart failure (HF) this force-frequency relationship (FFR) is often flattened or reversed. Although reduced sarcoplasmic reticulum Ca(2+)-ATPase function may be involved, decreased I(Ca) availability may also contribute. Longer action potential duration (APD), slower intracellular Ca(2+) concentration (Ca(2+)(i)) decline, and higher diastolic Ca(2+)(i) in HF could all slow I(Ca) recovery from inactivation, thereby decreasing I(Ca) availability. We measured the effect of different diastolic Ca(2+)(i) on I(Ca) inactivation and recovery from inactivation in rabbit cardiac myocytes. Both I(Ca) and Ba(2+) current (I(Ba)) were measured. I(Ca) decay was accelerated only at high diastolic Ca(2+)(i) (600 nM). I(Ba) inactivation was slower but insensitive to Ca(2+)(i). Membrane potential dependence of I(Ca) or I(Ba) availability was not affected by Ca(2+)(i) <600 nM. Recovery from inactivation was slowed by both depolarization and high Ca(2+)(i). We also used perforated patch with action potential (AP)-clamp and normal Ca(2+) transients, using various APDs as conditioning pulses for different frequencies (and to simulate HF APD). Recovery of I(Ca) following longer APD was increasingly incomplete, decreasing I(Ca) availability. Trains of long APs caused a larger I(Ca) decrease than short APD at the same frequency. This effect on I(Ca) availability was exacerbated by slowing twitch Ca(2+)(i) decline by approximately 50\%. We conclude that long APD and slower Ca(2+)(i) decline lead to cumulative inactivation limiting I(Ca) at high heart rates and might contribute to the negative FFR in HF, independent of altered Ca(2+) channel properties.

@article{Alta_2007_563, abstract = {Ca(2+) current (I(Ca)) recovery from inactivation is necessary for normal cardiac excitation-contraction coupling. In normal hearts, increased stimulation frequency increases force, but in heart failure (HF) this force-frequency relationship (FFR) is often flattened or reversed. Although reduced sarcoplasmic reticulum Ca(2+)-ATPase function may be involved, decreased I(Ca) availability may also contribute. Longer action potential duration (APD), slower intracellular Ca(2+) concentration ([Ca(2+)](i)) decline, and higher diastolic [Ca(2+)](i) in HF could all slow I(Ca) recovery from inactivation, thereby decreasing I(Ca) availability. We measured the effect of different diastolic [Ca(2+)](i) on I(Ca) inactivation and recovery from inactivation in rabbit cardiac myocytes. Both I(Ca) and Ba(2+) current (I(Ba)) were measured. I(Ca) decay was accelerated only at high diastolic [Ca(2+)](i) (600 nM). I(Ba) inactivation was slower but insensitive to [Ca(2+)](i). Membrane potential dependence of I(Ca) or I(Ba) availability was not affected by [Ca(2+)](i) <600 nM. Recovery from inactivation was slowed by both depolarization and high [Ca(2+)](i). We also used perforated patch with action potential (AP)-clamp and normal Ca(2+) transients, using various APDs as conditioning pulses for different frequencies (and to simulate HF APD). Recovery of I(Ca) following longer APD was increasingly incomplete, decreasing I(Ca) availability. Trains of long APs caused a larger I(Ca) decrease than short APD at the same frequency. This effect on I(Ca) availability was exacerbated by slowing twitch [Ca(2+)](i) decline by approximately 50\%. We conclude that long APD and slower [Ca(2+)](i) decline lead to cumulative inactivation limiting I(Ca) at high heart rates and might contribute to the negative FFR in HF, independent of altered Ca(2+) channel properties.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Altamirano, Julio and Bers, Donald M}, biburl = {https://www.bibsonomy.org/bibtex/2c1332533350fa7a8ae3de7d777be4cf4/hake}, description = {The whole bibliography file I use.}, doi = {10.1152/ajpheart.00469.2006}, file = {Alta_2007_563.pdf:Alta_2007_563.pdf:PDF}, institution = {Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Ave., Maywood, IL 60153, USA.}, interhash = {5281ba287d71a9537df384e7081cd9f8}, intrahash = {c1332533350fa7a8ae3de7d777be4cf4}, journal = {Am J Physiol Heart Circ Physiol}, keywords = {Action Animals; Calcium Calcium, Cardiac, Cells, Channel Channels, Contraction, Cultured; Gating, Ion L-Type, Myocardial Myocytes, Potentials, Rabbits metabolism; physiology;}, month = Jul, number = 1, pages = {H563--H573}, pdf = {Alta_2007_563.pdf}, pii = {00469.2006}, pmid = {17400724}, timestamp = {2009-06-03T11:20:58.000+0200}, title = {Effect of intracellular Ca2+ and action potential duration on L-type Ca2+ channel inactivation and recovery from inactivation in rabbit cardiac myocytes.}, url = {http://dx.doi.org/10.1152/ajpheart.00469.2006}, volume = 293, year = 2007 }