TY - JOUR
T1 - Time course of the increase in the myocardial slow inward current after a photochemically generated concentration jump of intracellular cAMP
AU - Nargeot, J.
AU - Nerbonne, J. M.
AU - Engels, J.
AU - Lester, H. A.
PY - 1983
Y1 - 1983
N2 - Voltage-clamped atrial trabeculae from bullfrog hearts were exposed to membrane-permeant photolyzable o-nitrobenzyl esters of cAMP and cGMP. UV flashes produced intracellular concentration jumps of cAMP or cGMP. With the cAMP derivative, flashes resulted in an increased slow inward current (I(si)), producing a broadened action potential. The I(si) reached a maximum 10-30 sec after the flash and decreased over the next 60-300 sec. The first increases were observable within 150 msec; this value is an upper limit imposed by the instrumentation. Responses to flashes lasted longer at high drug concentrations and in the presence of the phosphodiesterase inhibitor papaverine; effects of flashes developed and decreased faster at higher temperature. Although the amplitude of the I(si) was increased, its waveform and voltage sensitivity were not affected. Intracellular concentration jumps of cAMP failed to affect the muscarinic K+ conductance. There were no observable effects of cGMP concentration jumps. The data confirm (i) that cAMP regulates the I(si) and (ii) that the 5- to 10-sec delay between application of β-agonists and the onset of positive inotropic effects, observed in previous studies, has been correctly ascribed to events prior to the interaction between cAMP and protein kinase.
AB - Voltage-clamped atrial trabeculae from bullfrog hearts were exposed to membrane-permeant photolyzable o-nitrobenzyl esters of cAMP and cGMP. UV flashes produced intracellular concentration jumps of cAMP or cGMP. With the cAMP derivative, flashes resulted in an increased slow inward current (I(si)), producing a broadened action potential. The I(si) reached a maximum 10-30 sec after the flash and decreased over the next 60-300 sec. The first increases were observable within 150 msec; this value is an upper limit imposed by the instrumentation. Responses to flashes lasted longer at high drug concentrations and in the presence of the phosphodiesterase inhibitor papaverine; effects of flashes developed and decreased faster at higher temperature. Although the amplitude of the I(si) was increased, its waveform and voltage sensitivity were not affected. Intracellular concentration jumps of cAMP failed to affect the muscarinic K+ conductance. There were no observable effects of cGMP concentration jumps. The data confirm (i) that cAMP regulates the I(si) and (ii) that the 5- to 10-sec delay between application of β-agonists and the onset of positive inotropic effects, observed in previous studies, has been correctly ascribed to events prior to the interaction between cAMP and protein kinase.
UR - http://www.scopus.com/inward/record.url?scp=0542444666&partnerID=8YFLogxK
U2 - 10.1073/pnas.80.8.2395
DO - 10.1073/pnas.80.8.2395
M3 - Article
C2 - 6300914
AN - SCOPUS:0542444666
SN - 0027-8424
VL - 80
SP - 2395
EP - 2399
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8 I
ER -