Inotropic effects of Ca2+ channel agonist and antagonists in neuraminidase-treated left atria of rats.

The effects of removal of sialic acid from cardiac sarcolemma on contractile functions and on inotropic responses to Ca2+ channel agonist and antagonists were investigated in rat left atria. About 64% of the total sialic acid content of the left atria was removed during a 90 min exposure to neuraminidase (2 u ml-1). The removal of sialic acid neither affected the development of twitch tension induced by stimulation at a frequency of 0.5 Hz, nor altered the interval-dependent changes in contractility such as the force-frequency relationship and post rest contractions. The positive inotropic effects produced by isoprenaline, and by an increase in extracellular Ca2+ concentration were the same in the neuraminidase-treated preparations as those in the untreated preparations. Bay K 8644, a Ca2+ channel agonist, induced an increase in contractility in the neuraminidase-treated preparations comparable to that in the untreated ones. Neuraminidase treatment significantly attenuated the negative inotropic effects of verapamil and diltiazem, whereas it had no effect on that of nifedipine. The results indicate that sialic acid removal modifies neither the basal contractile functions nor the positive inotropism which is associated with an enhancement of the slow inward Ca2+ current. However, sialic acid, which constitutes the glycocalyx of the cardiac sarcolemma, may be involved in the mechanism of the Ca2+ channel antagonistic actions of verapamil and diltiazem, but not that of nifedipine. Thus, our results provide pharmacological evidence that verapamil and diltiazem behave differently from the dihydropyridine compounds.