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G Vassort

Publications and source records attributed to G Vassort.

140 records · Page 8Linked to original sources
PubMedDate not supplied

Signalling by protein kinase C isoforms in the heart.

Understanding transmembrane signalling process is one of the major challenge of the decade. In most tissues, since Fisher and Krebs's discovery in the 1950's, protein phosphorylation has been widely recognized as a key event of this cellular function. Indeed, binding of hormones or neurotransmitters to specific membrane receptors leads to the generation of cytosoluble second messengers which in turn activate a specific protein kinase. Numerous protein kinases have been so far identified and roughly classified into two groups, namely serine/threonine and tyrosine kinases on the basis of the target acid although some more recently discovered kinases like MEK (or MAP kinase kinase) phosphorylate both serine and tyrosine residues. Protein kinase C is a serine/threonine kinase that was first described by Takai et al. [1] as a Ca- and phospholipid-dependent protein kinase. Later on, Kuo et al. [2] found that PKC was expressed in most tissues including the heart. The field of investigation became more complicated when it was found that the kinase is not a single molecular entity and that several isoforms exist. At present, 12 PKC isoforms and other PKC-related kinases [3] were identified in mammalian tissues. These are classified into three groups. (1) the Ca-activated alpha-, beta-, and gamma-PKCs which display a Ca-binding site (C2); (2) the Ca-insensitive delta-, epsilon-, theta-, eta-, and mu-PKCs. The kinases that belong to both of these groups display two cysteine-rich domains (C1) which bind phorbol esters (for recent review on PKC structure, see [4]). (3) The third group was named atypical PKCs and include zeta, lambda, and tau-PKCs that lack both the C2 and one cysteine-rich domain. Consequently, these isoforms are Ca-insensitive and cannot be activated by phorbol esters [5]. In the heart, evidence that multiple PKC isoforms exist was first provided by Kosaka et at. [6] who identified by chromatography at least two PKC-related isoenzymes. Numerous studies were thus devoted to the biochemical characterization of these isoenzymes (see [7] for review on cardiac PKCs) as well as to the identification of their substrates. This overview aims at updating the present knowledge on the expression, activation and functions of PKC isoforms in cardiac cells.

Animals↗
PubMedDate not supplied

Aldosterone upregulates Ca(2+) current in adult rat cardiomyocytes.

Aldosterone is associated with the pathogenesis and progression of left ventricular hypertrophy and heart failure, independent of its relation with arterial blood pressure. However, little information exists about the possible influence of this mineralocorticoisteroid on cardiomyocyte electrical activity. The present study was designed to determine the role of aldosterone on whole-cell Ca(2+) current (I(Ca)) in isolated adult rat ventricular myocytes using the patch-clamp technique. We found that incubation of cells with 1 micromol/L aldosterone for 24 hours increases the density of I(Ca) significantly. This "long-term" aldosterone treatment had no significant effects on the kinetics and voltage dependence of I(Ca) inactivation. Moreover, no demonstrable influence of aldosterone on I(Ca) could be detected during short-term exposure (up to 6 hours), under our experimental conditions. The classical aldosterone intracellular receptor antagonist spironolactone (250-fold excess) was able to blunt the aldosterone-induced increase in I(Ca) density. These effects were also observed with lower concentrations of aldosterone (10 and 100 nmol/L). Moreover, inhibitors of transcription (actinomycin D, 5 microg/mL) and protein synthesis (cycloheximide, 20 microg/mL) prevented the aldosterone-dependent increase in I(Ca). Therefore, the long latency I(Ca) stimulation effect of aldosterone might result from an increased channel expression. We suggest that this genomic action contributes to the increased I(Ca) observed during cardiac remodeling.

Aldosterone↗
PubMedDate not supplied

Microtubule disruption modulates Ca(2+) signaling in rat cardiac myocytes.

Microtubules have been shown to alter contraction in cardiac myocytes through changes in cellular stiffness. However, an effect on excitation-contraction coupling has not been examined. Here we analyze the effects of microtubule disruption by 1 micromol/L colchicine on calcium currents (I(Ca)) and [Ca(2+)](i) transients in rat ventricular myocytes. I(Ca) was studied using the whole-cell patch-clamp technique. Colchicine treatment increased I(Ca) density (peak values, -4.6+/-0.4 and -9.1+/-1.3 pA/pF in 11 control and 12 colchicine-treated myocytes, respectively; P<0.05). I(Ca) inactivation was well fitted by a biexponential function. The slow component of inactivation was unchanged, whereas the fast component was accelerated after colchicine treatment (at -10 mV, 11.8+/-1.0 versus 6.7+/-1.0 ms in control versus colchicine-treated cells; P<0.005). [Ca(2+)](i) transients were analyzed by fluo-3 epifluorescence simultaneously with I(Ca). Peak [Ca(2+)](i) transients were significantly increased in cardiac myocytes treated with colchicine. The values of F/F(0) at 0 mV were 1.1+/-0.02 in 9 control cells and 1.4+/-0.1 in 11 colchicine-treated cells (P<0.05). beta-Adrenergic stimulation with 1 micromol/L isoproterenol increased both I(Ca) and [Ca(2+)](i) transient in control cells. However, no significant change was induced by isoproterenol on colchicine-treated cells. Colchicine and isoproterenol effects were similar and not additive. Inhibition of adenylyl cyclase by 200 micromol/L 2'-deoxyadenosine 3'-monophosphate blunted the colchicine effect. We suggest that beta-adrenergic stimulation and microtubule disruption share a common pathway to enhance I(Ca) and [Ca(2+)](i) transient.

Adenosine Monophosphate↗
PubMedDate not supplied

Sodium-calcium exchange in regulation of cardiac contraction.

The origin and possible regulatory mechanism of tonic tension (ICa-independent component of active contractile activity) were investigated in frog antrial muscle under voltage-clamp conditions. Replacement of NaCl by LiCl resulted in a fast decrease in tonic tension; a similar fast decrease of this contractile component was induced by Ca-free solution. When low Na Ringer's solution was applied, tonic tension increased transiently and then decreased to a steady amplitude; at return to normal Ringer's, a further, substantial decrease in tonic tension occurred before the original level was reached. Similar behavior of tonic tension was observed when both [Na] o and [Ca]o were lowered, but the ratio [Ca]o/[Na]o2 remained constant; the transient changes were prevented by using low Ca and Na solutions and keeping the ratio of [Ca]o/[Na]o5 constant. The significance of Na-Ca exchange in regulating tonic tension and the possibility that this exchange may be electrogenic are discussed.

Animals↗
PubMedDate not supplied

Relaxation of frog myocardium.

Tension fall of frog heart contraction was analyzed under voltage-clamp conditions. It appears mostly exponential. The rate of relaxation depends upon the extracellular and intracellular Na concentrations. This suggests that the relaxation is under the control of Na-Ca exchange. The speeding up of relaxation by adrenaline in frog heart is revealed by low Na solution, while it is hidden by the primordial Na-Ca exchange in Ringer's solution.

Animals↗