TY - JOUR
T1 - α-Adrenergic modification of the Ca2+ transient and contraction in single rat cardiomyocytes
AU - O'Rourke, Brian
AU - Reibel, Diane K.
AU - Thomas, Andrew P.
N1 - Funding Information:
This work was supported by Public Health Service research grants AA-07 186, DK-38422 and HL-30945, and Federal ing Grant 5-232T-HL-07599-04.
PY - 1992/8
Y1 - 1992/8
N2 - Intracellular Ca2+ transients and contraction were measured simultaneously in single rat cardiomyocytes loaded with the flurorescent Ca2+ indicator fura-2, using a recently described high-speed digital imaging method (O'Rourke et al., 1990, Am J Physiol 259: H230-H242). In cardiomyocytes electrically-stimulated at Hertz, α-adrenoceptor activation in the presence of β-adrenoceptor blockade resulted in enhanced cell shortening associated with an increase in the amplitude of the cytosolic Ca2+ transient. Both effects developed in parallel over a 10-min time period and occurred without a change in the half-times for decay of Ca2+ or relaxation of the cell. To determine if the increase in contactility was proportional to the increase in peak cytosolic Ca2+, the effect of raising extracellular Ca2+ ([Ca2+]0) from 0.5 to 3 mm was examined in the absence and presence of α-adrenoceptor activation. At [Ca2+]0 concentrations up to 1 mm, α-adrenoceptor-mediated effects on contraction were directly correlated with changes in peak cytosolic Ca2+ and resembled the effect of raising [Ca2+]0 alone. In 2 and 3 mm [Ca2+]0, peak cytosolic Ca2+ approached a maximal level and α-adrenoceptor activation induced a slight enhancement in the extent of shortening in the absence of a detectable alteration of the Ca2+ transient. In contrast, under similar conditions, β-adrenergic effects on shortening never exceeded those of α-adrenoceptor activation, although much higher peak cytosolic Ca2+ concentrations were achieved at high [Ca2+]0. The results suggest that the mechanism underlying the positive inotropic effect of α-adrenergic stimulation in rat ventricular cells is primarily dependent on an enhancement of the cytosolic Ca2+ transient, although there is also an increase in the myofibrillar response to intracellular Ca2+ under the condition of high extracellular Ca2+.
AB - Intracellular Ca2+ transients and contraction were measured simultaneously in single rat cardiomyocytes loaded with the flurorescent Ca2+ indicator fura-2, using a recently described high-speed digital imaging method (O'Rourke et al., 1990, Am J Physiol 259: H230-H242). In cardiomyocytes electrically-stimulated at Hertz, α-adrenoceptor activation in the presence of β-adrenoceptor blockade resulted in enhanced cell shortening associated with an increase in the amplitude of the cytosolic Ca2+ transient. Both effects developed in parallel over a 10-min time period and occurred without a change in the half-times for decay of Ca2+ or relaxation of the cell. To determine if the increase in contactility was proportional to the increase in peak cytosolic Ca2+, the effect of raising extracellular Ca2+ ([Ca2+]0) from 0.5 to 3 mm was examined in the absence and presence of α-adrenoceptor activation. At [Ca2+]0 concentrations up to 1 mm, α-adrenoceptor-mediated effects on contraction were directly correlated with changes in peak cytosolic Ca2+ and resembled the effect of raising [Ca2+]0 alone. In 2 and 3 mm [Ca2+]0, peak cytosolic Ca2+ approached a maximal level and α-adrenoceptor activation induced a slight enhancement in the extent of shortening in the absence of a detectable alteration of the Ca2+ transient. In contrast, under similar conditions, β-adrenergic effects on shortening never exceeded those of α-adrenoceptor activation, although much higher peak cytosolic Ca2+ concentrations were achieved at high [Ca2+]0. The results suggest that the mechanism underlying the positive inotropic effect of α-adrenergic stimulation in rat ventricular cells is primarily dependent on an enhancement of the cytosolic Ca2+ transient, although there is also an increase in the myofibrillar response to intracellular Ca2+ under the condition of high extracellular Ca2+.
KW - Cytosolic Ca transient
KW - Excitation-contraction coupling
KW - Fluorescence imaging
KW - Inotropy
KW - fura-2
KW - α-adrenergic receptor
KW - β-adrenergic receptor
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U2 - 10.1016/0022-2828(92)91095-M
DO - 10.1016/0022-2828(92)91095-M
M3 - Article
C2 - 1331471
AN - SCOPUS:0026661076
VL - 24
SP - 809
EP - 820
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 8
ER -