Role of cyclic nucleotide-dependent actin cytoskeletal dynamics:Ca(2+)](i) and force suppression in forskolin-pretreated porcine coronary arteries.

Hocking KM, Baudenbacher FJ, Putumbaka G, Venkatraman S, Cheung-Flynn J, Brophy CM, Komalavilas P
PLoS One. 2013 8 (4): e60986

PMID: 23593369 · PMCID: PMC3625185 · DOI:10.1371/journal.pone.0060986

Initiation of force generation during vascular smooth muscle contraction involves a rise in intracellular calcium ([Ca(2+)]i) and phosphorylation of myosin light chains (MLC). However, reversal of these two processes alone does not account for the force inhibition that occurs during relaxation or inhibition of contraction, implicating that other mechanisms, such as actin cytoskeletal rearrangement, play a role in the suppression of force. In this study, we hypothesize that forskolin-induced force suppression is dependent upon changes in actin cytoskeletal dynamics. To focus on the actin cytoskeletal changes, a physiological model was developed in which forskolin treatment of intact porcine coronary arteries (PCA) prior to treatment with a contractile agonist resulted in complete suppression of force. Pretreatment of PCA with forskolin suppressed histamine-induced force generation but did not abolish [Ca(2+)]i rise or MLC phosphorylation. Additionally, forskolin pretreatment reduced filamentous actin in histamine-treated tissues, and prevented histamine-induced changes in the phosphorylation of the actin-regulatory proteins HSP20, VASP, cofilin, and paxillin. Taken together, these results suggest that forskolin-induced complete force suppression is dependent upon the actin cytoskeletal regulation initiated by the phosphorylation changes of the actin regulatory proteins and not on the MLC dephosphorylation. This model of complete force suppression can be employed to further elucidate the mechanisms responsible for smooth muscle tone, and may offer cues to pathological situations, such as hypertension and vasospasm.

MeSH Terms (20)

Actin Cytoskeleton Actin Depolymerizing Factors Actins Animals Biomechanical Phenomena Calcium Cell Adhesion Molecules Colforsin Coronary Vessels Histamine HSP20 Heat-Shock Proteins Intracellular Space Microfilament Proteins Muscle Contraction Myosin Light Chains Nucleotides, Cyclic Paxillin Phosphoproteins Phosphorylation Sus scrofa

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