Relationship between dibutyryl cyclic AMP and microtubule organization in contracting heart muscle cells

Rhythmic and synchronous contractions of interconnecting myocyte cultures prepared from fetal rat hearts are arrested upon the addition of 0.2--2.0 mM N6, O2'-dibuturyladenosine 3':5'-cyclic monophosphate (Bt2cAMP). The contractions arrested by Bt2cAMP are restored either by diluting the Bt2cAMP from the media or by adding colchicine. While colchicine restores Bt2cAMP-arrested myocyte contractions at concentrations as low as 1.0 micron, the inactive isomer lumicolchicine shows no effect. Morphologically, Bt2cAMP treatment of myocyte cultures results in the appearance of numerous elongated cellular processes not present in control cultures. Ultrastructural examination indicates that in Bt2cAMP-treated cells the intracellular distribution of microtubules is altered such that these organelles appear to accumulate in parallel arrays. In cells not treated with Bt2cAMP, the microtubules appear randomly oriented, while in cells treated with only colchicine, intact microtubules are not observed. The relationship between microtubules an heart cell contraction is discussed.