TY - JOUR
T1 - Relative roles of intracellular Ca2+ and pH in shaping myocardial contractile response to acute respiratory alkalosis
AU - Kusuoka, H.
AU - Backx, P. H.
AU - Camilion de Hurtado, M. C.
AU - Azan-Backx, M.
AU - Marban, E.
AU - Cingolani, H. E.
PY - 1993
Y1 - 1993
N2 - During acute respiratory alkalosis, myocardial contractility initially increases but then declines toward control levels. To elucidate the mechanism of this response, two parallel strategies were adopted: isovolumic left ventricular developed pressure (DP) and intracellular pH (pH(i)) were measured in isolated ferret hearts using 31P-nuclear magnetic-resonance spectroscopy, and isometric developed tension (DT) and intracellular Ca2+ concentration ([Ca2+](i)) were measured in ferret papillary muscles using microinjected fura 2 salt. When hypocapnia was induced by sudden introduction of perfusate equilibrated with 2% CO2 (from 5% CO2 in control), DP increased to a maximum of 120 ± 3% (SE; n = 7) of control within 40 s. Afterward, DP decreased toward control levels, reaching a new steady state in 2-3 min. In contrast, pH(i) increased from control (7.11 ± 0.01) only after 30 s of hypocapnia and reached a peak of 7.25 ± 0.02 between 80 and 100 s. Thus pH(i) lagged behind contractility. In contrast to pH(i), [Ca2+](i) changed in parallel with DT; when DT reached a maximum (251 ± 63% of control; n = 5) during hypocapnia, the amplitude of [Ca2+](i) transients also peaked (190 ± 22% of control; n = 5). A simulation of contractile force based on our measurements of pH(i) and [Ca2+](i) along with published Ca2+-tension relations, described adequately the changes in developed force during hypocapnia. These results indicate that the biphasic changes in [Ca2+](i), coupled with an out-of-phase change in pH(i), underlie the biphasic response of myocardial contractility to hypocapnia.
AB - During acute respiratory alkalosis, myocardial contractility initially increases but then declines toward control levels. To elucidate the mechanism of this response, two parallel strategies were adopted: isovolumic left ventricular developed pressure (DP) and intracellular pH (pH(i)) were measured in isolated ferret hearts using 31P-nuclear magnetic-resonance spectroscopy, and isometric developed tension (DT) and intracellular Ca2+ concentration ([Ca2+](i)) were measured in ferret papillary muscles using microinjected fura 2 salt. When hypocapnia was induced by sudden introduction of perfusate equilibrated with 2% CO2 (from 5% CO2 in control), DP increased to a maximum of 120 ± 3% (SE; n = 7) of control within 40 s. Afterward, DP decreased toward control levels, reaching a new steady state in 2-3 min. In contrast, pH(i) increased from control (7.11 ± 0.01) only after 30 s of hypocapnia and reached a peak of 7.25 ± 0.02 between 80 and 100 s. Thus pH(i) lagged behind contractility. In contrast to pH(i), [Ca2+](i) changed in parallel with DT; when DT reached a maximum (251 ± 63% of control; n = 5) during hypocapnia, the amplitude of [Ca2+](i) transients also peaked (190 ± 22% of control; n = 5). A simulation of contractile force based on our measurements of pH(i) and [Ca2+](i) along with published Ca2+-tension relations, described adequately the changes in developed force during hypocapnia. These results indicate that the biphasic changes in [Ca2+](i), coupled with an out-of-phase change in pH(i), underlie the biphasic response of myocardial contractility to hypocapnia.
KW - hypocapnia
KW - intracellular calcium concentration
KW - intracellular pH
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U2 - 10.1152/ajpheart.1993.265.5.h1696
DO - 10.1152/ajpheart.1993.265.5.h1696
M3 - Article
C2 - 8238582
AN - SCOPUS:0027491605
VL - 265
SP - H1696-H1703
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 5 34-5
ER -