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Mechanisms Associated with the Negative Inotropic Effect of Deuterium Oxide in Single Rat Ventricular Myocytes
Author(s) -
Hongo K.,
Brette F.,
Haroon M. M.,
White E.
Publication year - 2000
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1111/j.1469-445x.2000.01935.x
Subject(s) - inotrope , myofilament , contraction (grammar) , chemistry , medicine , myocyte , intracellular , cardiac muscle , endocrinology , contractility , biophysics , biology , biochemistry
Deuterium oxide (D2O) is known to cause a negative inotropic effect in muscle although the mechanisms associated with this response in cardiac muscle are not well understood. We studied the effects of D2O in single rat ventricular myocytes in order to characterise the mechanisms associated with its negative inotropic effect and to assess its possible use as an acute modulator of microtubules. D2O rapidly reduced the magnitude of contraction in rat ventricular myocytes, and there was some recovery of contraction in the presence of D2O. Colchicine, an agent known to depolymerise microtubules, did not modify the effect of D2O. D2O decreased the L‐type Ca 2+ current (ICa), measured under whole cell and perforated patch clamp conditions. Slowing of the time to peak and a delay in inactivation of ICa were observed. Intracellular calcium ([Ca 2+ ] i ) and sodium ([Na+] i ) were measured using the fluorescent indicators fura‐2 and SBFI, respectively. The fall in contraction upon exposure to D2O was not associated with a fall in the [Ca 2+ ] i transient; this response is indicative of a reduction in myofilament Ca 2+ sensitivity. Both the [Ca 2+ ] i transient and [Na+] i increased during the partial recovery of contraction in the presence of D2O. We conclude that a decrease in the myofilament sensitivity for Ca 2+ and a reduction in Ca 2+ influx via ICa are principally responsible for the negative inotropic effect of D2O in cardiac muscle. We found no evidence to explain the negative inotropic effect of D2O in terms of microtubule proliferation. In addition we suggest that acute application of D2O is not a useful procedure for the investigation of the role of microtubules in excitation‐contraction coupling in cardiac muscle.