Biomedical subjects

G Mostacciuolo

Publications and source records attributed to G Mostacciuolo.

4 recordsLinked to original sources

PubMed2006

Rate dependency of beta-adrenergic modulation of repolarizing currents in the guinea-pig ventricle.

Beta-adrenergic stimulation modulates ventricular currents and sinus cycle length (CL). We investigated how changes in CL affect the current induced by isoprenaline (Iso) during the action potential (AP) of guinea-pig ventricular myocytes. Action-potential clamp was applied at CLs of 250 and 1000 ms to measure: (1) the net current induced by 0.1 microm Iso (I(Iso)); (2) the L-type Ca2+ current I(CaL) and slow delayed rectifier current I(Ks) components of I(Iso) (I(IsoCa) and I(IsoK)), identified as the Iso-induced current sensitive to nifedipine and HMR1556, respectively; and (3) I(Iso) persisting after inhibition of both I(Ca) and I(Ks) (I(isoR)). The pause dependency of I(Ks) and its modulation were evaluated in voltage-clamp experiments. The rate dependency of the duration of the action potential at 90% repolarization (APD90) and its modulation by isoprenaline were tested in current-clamp experiments. At a CL of 250 ms I(Iso) was inward during initial repolarization and reversed at 59% of APD90. At a CL of 1000 ms I(Iso) became mostly inward in all cells. Switching to shorter CL did not change I(IsoCa) and I(IsoK) amplitudes, but moved their peak amplitudes to earlier repolarization; I(IsoR) was independent of CL. Acceleration of I(IsoK) at shorter CL was based on faster pause dependency of I(Ks) activation rate. The 'restitution' of activation rates was modulated by isoprenaline. The APD90-CL relation was rotated anticlockwise by isoprenaline and crossed the control curve at a CL of 150 ms (400 beats min(-1)). We conclude that: (1) isoprenaline induced markedly different current profiles according to pacing rate, involving CL-dependent I(Ca) and I(Ks) modulation; (2) the effect of isoprenaline on APD90 was CL dependent, and negligible during tachycardia; and (3) during sympathetic activation, repolarization stability may involve matched modulation of sinus rate and repolarizing currents.

Action Potentials↗

PubMed2003

Diverse toxicity associated with cardiac Na+/K+ pump inhibition: evaluation of electrophysiological mechanisms.

(E,Z)-3-((2-Aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744) is a novel Na(+)/K(+) pump inhibitor with positive inotropic effects. Compared with digoxin in various experimental models, PST2744 was consistently found to be less arrhythmogenic, thus resulting in a significantly higher therapeutic index. The present work compares the electrophysiological effects of PST2744 and digoxin in guinea pig ventricular myocytes, with the aim to identify a mechanism for their different toxicity. The work showed that 1) the action potential was transiently prolonged and then similarly shortened by both agents; 2) the ratio between Na(+)/K(+) pump inhibition and inotropy was somewhat larger for PST2744 than for digoxin; 3) both agents accelerated inactivation of high-threshold Ca(2+) current (I(CaL)), without affecting its peak amplitude; 4) the transient inward current (I(TI)) induced by a Ca(2+) transient in the presence of complete Na(+)/K(+) pump blockade was inhibited (-43%) by PST2744 but not by digoxin; 5) the conductance of Na(+)/Ca(2+) exchanger current (I(NaCa)), recorded under Na(+)/K(+) pump blockade, was only slightly inhibited by PST2744 (-14%) and unaffected by digoxin; and 6) both agents inhibited delayed rectifier current I(Ks) (<or=-21%); delayed rectifier current I(Kr) was inhibited by PST2744 only, but the effect was marginal (-6%). Thus, 1) the higher therapeutic index of PST2744 may be accounted for by inhibition of I(TI), a current directly involved in digitalis-induced arrhythmias. Indeed, the other differences observed concern quantitatively small effects; and 2) I(TI) suppression by PST2744 may be only partly accounted for by inhibition of the Na(+)/Ca(2+) exchanger.

Animals↗

PubMed1988

A voltage-dependent calcium current in mouse Swiss 3T3 fibroblasts.

Patch-clamp experiments in the whole-cell mode have been performed in Swiss 3T3 mouse fibroblasts. Depolarizations from negative holding potential (Vh less than -60 mV) gave rise to a rapidly activating, fully inactivating, inward current of few tenths of nA in physiological saline at 35 degrees C. The current persisted when external Na+ was replaced by impermeant TMA+ and disappeared in 0 Ca2+, 1 mM EGTA. The current was reversible blocked by Co2+ and it was slightly reduced when external Ca2+ was substituted by Ba2+. Finally its reversal potential changed with Nernstian slope with increasing external Ca2+ concentrations. It is concluded that these cells possess a voltage-dependent Ca2+ channel.

Animals↗

PubMed1987

Single- and multi-channel currents recorded with patch electrodes in mouse eggs.

Zona-free mouse eggs are amenable to patch recording as well as to whole-cell recording (Bland et al., 1984; Peres, 1986a). Although many patches are silent, others show spontaneous channel opening; the single channel current is 1.5 pA and inwardly directed at resting potential (RP). Current amplitudes distribute normally as a single population at RP, however at RP-50 mV the amplitude histogram indicates two channel populations. Open time distribution is exponential with a mean open time between 4 and 7 msec at RP. In three cases out of thirty-eight, in which depolarizations were given from a holding potential of RP-50 mV, microscopic currents very similar in kinetics and voltage-dependence to the whole-cell Ca2+ current were observed. No single-channel currents could be resolved in these traces. The results reported here indicate that the voltage-dependent Ca2+ current of the mouse egg goes through low-conductance channels located in high density spots on the egg surface.

Animals↗