Involvement of Ca2+ buffering and Na+/Ca2+ exchange in the positive staircase of contraction in guinea-pig ventricular myocytes.
The mean sarcomere length (SL) of guinea-pig cardiac myocytes was recorded simultaneously with the whole-cell current under voltage-clamp conditions. After blocking both sarcoplasmic reticulum (SR) and L-type Ca(2+) channels with ryanodine, cyclopiazonic acid and nicardipine, strong depolarizing pulses induced only the tonic component of SL shortening through the reverse mode of Na(+)/Ca(2+) exchange (NCX). A positive staircase of SL shortening was observed on applying a train pulses to +60~+100 mV at 2 Hz and trans-membrane Ca(2+) flux was calculated from the time integral of the Na(+)/Ca(2+) exchange current ( I(NCX)). Changes in cytosolic [Ca(2+)] ([Ca(2+)](i)) were determined indirectly using the experimental [Ca(2+)](i)/SL relationship. Cellular Ca(2+) buffering was characterized by a lumped single-component system with a maximum binding capacity of 200 micro M and a dissociation constant of 613 nM. Despite the decrease in driving force, the amplitude of the outwards I(NCX) at +60 mV gradually increased along with the positive staircase. The model simulation suggested that this increase of outwards I(NCX) is caused by a dramatic increase in Ca(2+)-mediated activation of NCX.
Kuratomi
S
S
Department of Physiology and Biophysics, Kyoto University Graduate School of Medicine, Sakyo-ku, 606-8501 Kyoto, Japan. kuratomi@card.med.kyoto-u.ac.jp
Matsuoka
S
S
Sarai
N
N
Powell
T
T
Noma
A
A
D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology; D006168:Guinea Pigs; D006352:Heart Ventricles; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
D002021:Buffers; D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D002118:Calcium