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(Circulation Research. 2001;89:e31.)
© 2001 American Heart Association, Inc.

Letters to the Editor

A Unifying Mechanism for the Role of Microtubules in the Regulation of [Ca²⁺]_i and Contraction in the Cardiac Myocyte

Sarah Calaghan, Ed White, Jean-Yves Le Guennec

School of Biomedical Sciences, University of Leeds, Leeds, UK, s.c.calaghan@leeds.ac.uk
Nutrition, Croissance, Cancer EA2103, University of Tours, Tours, France

To the Editor:

There is evidence to show that in the absence of prior microtubule proliferation, disruption of the microtubule cytoskeleton by colchicine does not significantly modulate cardiac contractility^1–8 or the intracellular Ca²⁺ ([Ca²⁺]_i) transient.⁸ These negative observations would not be interesting by themselves, unless it had also been shown that in those models of pressure-overload hypertrophy that result in proliferation of microtubules, colchicine normalizes depressed contractility, and that chemical proliferation of the microtubules by taxol in normal myocytes decreases both contraction^1,7,9 and the [Ca²⁺]_i transient.⁹

Recent debate in Circulation Research was sparked by the work of Gómez et al.¹⁰ Surprisingly, this group reported that colchicine increased the global [Ca²⁺]_i transient and I_Ca,L in the normal cardiocyte.^10,11 Unless colchicine decreases myofilament Ca²⁺ sensitivity to the exact degree required to offset changes in [Ca²⁺]_i, colchicine would be expected to increase contractility in the normal myocyte. Gómez et al¹⁰ suggested that the increase in [Ca²⁺]_i they saw was due to stimulation of adenylyl cyclase via increased intracellular free tubulin, although cAMP, the product of adenylyl cyclase stimulation, does not increase in response to colchicine in normal or hypertrophied cardiac muscle.⁸ In a study in which we measured contraction and [Ca²⁺]_i, as well as I_Ca,L,¹² we were unable to reproduce the results of Gómez et al¹⁰ in the intact cardiac cell.

In their response, Kerfant et al¹¹ were critical of our study,¹² but unfortunately did not take the opportunity to discuss the apparent discrepancies that exist . . . [Full Text of this Article]