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E Stjärne

Publications and source records attributed to E Stjärne.

At least 19 recordsLinked to original sources
PubMed1995

Geometry, kinetics and plasticity of release and clearance of ATP and noradrenaline as sympathetic cotransmitters: roles for the neurogenic contraction.

The paper compares the microphysiology of sympathetic neuromuscular transmission in three model preparations: the guinea-pig and mouse vas deferens and rat tail artery. The first section describes the quantal release of ATP and noradrenaline from individual sites. The data are proposed to support a string model in which: (i) most sites (> or = 99%) ignore the nerve impulse and a few (< or = 1%) release a single quantum of ATP and noradrenaline; (ii) the probability of monoquantal release is extremely non-uniform; (iii) high probability varicosities form 'active' strings; and (iv) an impulse train causes repeated quantal release from these sites. Analogy with molecular mechanisms regulating transmitter exocytosis in other systems is proposed to imply that coincidence of at least two factors at the active zone, Ca2+ and specific cytosolic protein(s), may be required to remove a 'fusion clamp', form a 'fusion complex' and trigger exocytosis of a sympathetic transmitter quantum, and that the availability of these proteins may regulate the release probability. The second section shows that clearance of noradrenaline in rat tail artery is basically > or = 30-fold slower than of co-released ATP, and that saturation of local reuptake and binding to local buffering sites maintain the noradrenaline concentration at the receptors, in spite of a profound decline in per pulse release during high frequency trains. The third section describes differences in the strategies by which mouse vas deferens and rat tail artery use ATP and noradrenaline to trigger and maintain the neurogenic contraction.

Adenosine Triphosphate↗
PubMed1994

Spatiotemporal pattern of quantal release of ATP and noradrenaline from sympathetic nerves: consequences for neuromuscular transmission.

The recent explosive development in research concerning the fundamental mechanisms of synaptic transmission helps put the present paper in context. It is now evident that not all transmitter vesicles in a nerve terminal, not even all those docked at its active zones, are immediately available for release (36). We watch, fascinated, the unraveling of the amazingly complex cellular mechanisms and molecular machinery that determine whether or not a vesicle is "exocytosis-competent" (77,78,39,79). Studies on quantal release in different systems show that neurons are fundamentally similar in one respect: that transmitter release from individual active zones is monoquantal (2). But they also show that active zones in different neurons differ drastically in the probability of monoquantal release and in the number of quanta immediately available for release (3). This implies that one should not extrapolate directly from transmitter release in one set of presynaptic terminals (e.g., in neuromuscular endplate or squid giant synapse) to that in other nerve terminals, especially if they have a very different morphology. As shown here, one should not even extrapolate from transmitter release in sympathetic nerves in one tissue (e.g., rat tail artery) to that in other tissues or species (e.g., mouse vas deferens). It is noteworthy that most studies of quantal release are based on electrophysiological analysis and therefore deal with release of fast, ionotropic transmitters from small synaptic vesicles at the active zones, especially in neurons in which these events may be examined with high resolution (49,48,46,33,32). Such data are useful as general models of the release of both fast and slow transmitters from small synaptic vesicles at active zones in other systems, provided that these transmitters are released in parallel, as are apparently ATP and NA in sympathetic nerves. They tell us little or nothing, however, about the release of transmitters (e.g., neuropeptides) from the large vesicles, nor about the spatiotemporal pattern of monoquantal release from small synaptic vesicles in the many neurons that have boutons-en-passent terminals. They show that the time course of effector responses to fast, rapidly inactivated transmitters such as ACh or ATP is necessarily release related. But they do not even address the possibility that the effector responses to slow transmitters such as NA, co-released from the same terminals, may obey completely different rules and perhaps rather be clearance related (7).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1991

K+ and Ca2+ channel blockers may enhance or depress sympathetic transmitter release via a Ca(2+)-dependent mechanism "upstream" of the release site.

Extracellular recording of the pre- and postjunctional electrical activity in guinea-pig or mouse vas deferens or rat tail artery was employed to study the mechanisms by which the K+ channel blockers, tetraethylammonium and 4-aminopyridine and the Ca2+ channel blockers, Cd2+, Mn2+ or nifedipine influence the nerve stimulation-induced release of adenosine 5'-triphosphate as a sympathetic co-transmitter. The K+ and Ca2+ channel blocking agents examined had no effect on the spontaneous quantal release of adenosine 5'-triphosphate. However, addition of tetraethylammonium and 4-aminopyridine inside the recording electrode broadened the nerve terminal action potential and caused it to become more resistant to local application of tetrodotoxin, and dramatically increased the magnitude and tetrodotoxin resistance of adenosine 5'-triphosphate release within the patch. Surprisingly, tetraethylammonium and 4-aminopyridine were equally effective when added outside the recording electrode; now they did not increase the duration of the nerve terminal action potential inside the patch but increased its resistance to locally applied tetrodotoxin and dramatically increased the magnitude as well as the tetrodotoxin resistance of adenosine 5'-triphosphate release from sites inside the patch. Both tetraethylammonium and 4-aminopyridine contributed to these effects, with a strong potentiating interaction. Nifedipine was without effect, but application of 1-100 microM Cd2+ or 1-5 mM Mn2+ either inside or outside the recording electrode blocked adenosine 5'-triphosphate release inside the patch. The results indicate: (i) that the nerve terminal action potential is generated by activation of voltage-gated, regenerative Na+ channels but also has a small component carried by influx of Ca2+ and that it is "normally" terminated by activation of voltage- as well as Ca(2+)-dependent K+ channels; (ii) that the release probability is tonically depressed by the resting K+ efflux, and promoted by the resting Ca2+ influx, "upstream" of the release sites; and (iii) that the upstream control of the release probability may involve both changes in properties of ionic channels in the nerve terminal membrane, and effects on the cytoskeleton leading to changes in the availability of releasable quanta in varicosities within the patch.

4-Aminopyridine↗
PubMed1990

"Upstream" regulation of the release probability in sympathetic nerve varicosities.

The results appear to support the following tentative working hypothesis. (1) Nerve impulse-induced transmitter release from sympathetic nerve varicosities is monoquantal and highly intermittent (probability range: 0-0.03). (2) Nerve impulses invade varicosities as all-or-none, Na+ channel-dependent action potentials; invasion failure may be rare. (3) The release probability is not controlled by properties (amplitude or duration) of the invading action potential or the resulting Ca2+ current, but by the availability of an as yet unidentified permissive factor. (4) The permissive factor is actively transported intra-axonally, probably in association with organelles (LDVs?). (5) The activation and/or transport of the permissive factor are controlled "upstream" of the varicosity; they depend on Ca2+ influx through channels insensitive to nifedipine (hence, not of L-type) but blocked by Cd2+ and apparently opened by slight depolarization of the resting membrane, in this respect behaving more as T- than N-type channels. (6) A high resting K+ efflux "upstream" of the varicosity restricts the availability of the permissive factor; it is the main mechanism maintaining the (economically necessary) low release probability. (7) Prejunctional agonists do not inhibit transmitter secretion by causing a conduction block or by reducing the action potential-induced Ca2+ influx into the varicosity itself, but by depressing the Ca2(+)-dependent activation and/or transport of the permissive factor; they act at least in part via receptors "upstream" of the varicosity. (8) This hypothesis for regulation of the release probability in sympathetic nerves may apply, at least in part, to other neurons as well.

Animals↗
PubMed1990

Presynaptic receptors and modulation of noradrenaline and ATP secretion from sympathetic nerve varicosities.

Our results in the model tissues examined show (1) that alpha 2 agonist(s) depressed the secretion of NA and ATP caused by nerve stimulation at low frequency, (2) that the secretion of both NA and ATP was moderately autoinhibited, under conditions when endogenous NA was shown to accumulate extracellularly, (3) that a K+ channel blocking agent increased much more strongly than alpha 2-adrenoceptors block the secretion of both NA and ATP, and also amplified enormously the NA-mediated neurogenic contraction, (4) that, therefore, a high K+ efflux is likely to be much more important than alpha 2-adrenoceptor-mediated autoinhibition for maintaining a low release probability in sympathetic nerve varicosities, and (5) that the alpha 2-adrenoceptor agonist, clonidine, or the Ca2+ channel blocking agent, Cd2+, inhibited transmitter secretion, at least in part, via targets "upstream" of the varicosity.

Adenosine Triphosphate↗
PubMed1989

Basic features of an extracellular recording method to study secretion of a sympathetic co-transmitter, presumably ATP.

An extracellular recording method is described which permits in suitable model tissues (e.g. guinea-pig or mouse vas deferens) study of the nerve impulse in sympathetic terminals and the release of transmitter from sites inside or outside the recording electrode. Negative- or positive-going potentials were assumed to reflect the excitatory junction current (EJC) caused by transmitter released inside or outside the electrode, respectively, and hence termed 'EJCi' (i for inside) or 'EJCo' (o for outside). The EJCo were shown to be Ca2+-dependent, blocked by addition of tetrodotoxin or guanethidine, resistant to the alpha 1-adrenoceptor blocking agent prazosin but suppressed by desensitization of P2-purinoceptors by alpha,beta-methylene ATP, and hence, presumably, are caused by release of ATP as a sympathetic co-transmitter. The amplitude of the EJCo was voltage-dependent and increased with the length and frequency of stimulus trains within the range of 1-50 shocks at 0.1-2.5 Hz. In conclusion, combined use of EJCi and EJCo provides a useful tool for physiological and pharmacological analysis of pre- and post-junctional events associated with the secretion of a sympathetic co-transmitter, presumably ATP.

Action Potentials↗
PubMed1989

Some pharmacological applications of an extracellular recording method to study secretion of a sympathetic co-transmitter, presumably ATP.

Extracellular recording in guinea-pig or mouse vas deferens or rat tail artery was used to study the effects of some pharmacological agents on the nerve terminal spike (NTS) and the secretion of a sympathetic co-transmitter (presumably ATP), as reflected in the excitatory junction current (EJC). A negative-going EJCi (i for inside) was assumed to reflect release from sites inside, and a positive-going EJCo (o for outside) release from sites outside the recording electrode. Passage into or out of the electrode seemed to be slow. Tetrodotoxin (TTX) in the outer medium blocked the NTS and ECJo as well as EJCi; TTX in the pipette blocked stimulus-evoked but not spontaneous EJCi. The dihydropyridine Ca2+ channel blocking agent, nifedipine, was without effect, but Cd2+ in the external medium blocked EJCo and also, by an effect apparently 'upstream' of varicosities, inhibited EJCi (i.e. release within the patch) but not the NTS. When present in the outer medium the alpha 2-adrenoceptor agonists, clonidine and xylazine, blocked both EJCo and EJCi, but not the NTS. The effects of clonidine were blocked by yohimbine, which in itself increased the EJCo by about 50%. Neuropeptide Y and met-enkephalin in the outer medium blocked EJCo; the effect of met-enkephalin was blocked by naloxone. The K+ channel blocking agents, tetraethylammonium and 4-aminopyridine, inside or outside the electrode, increased dramatically the size of EJCi or EJCo, respectively.

Action Potentials↗