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Biomedical subjects

B A Kotsias

Publications and source records attributed to B A Kotsias.

At least 19 recordsLinked to original sources
PubMed2001

Sodium influx during action potential in innervated and denervated rat skeletal muscles.

Resting Na(+) influx (J(i)(Na)) was measured in innervated and denervated (1-6 days) rat extensor digitorum longus muscle in the absence and presence of 2 micromol/L tetrodotoxin (TTX). The mean value of Na(+) permeability (P(Na)) in innervated muscles was 49.6 +/- 2.6 pm.s(-1). At the second day postdenervation, it decreased by about 45%. This was followed, between the second and fourth days, by a sharp rise, which by the sixth day reached a steady value approximately 2.5 times greater than that of innervated muscles. This, most likely, generated the 30% increase in internal [Na(+)] concentration ([Na(+)](I)) observed at this time. Tetrodotoxin reduced P(Na) of both innervated and denervated muscles by about 25%. In 6-day denervated muscles, virtually all the TTX effect on P(Na) represents the blockage of TTX-resistant Na(+) channels. Denervation produced a depolarization of about 20 mV by the sixth day. The extra J(i)(Na) per action potential (AP) decreased monotonically with time after denervation from 20.0 +/- 3.8 in innervated to 11.1 +/- 1.0 nmol.g(-1).AP(-1) in 6-day denervated muscles. The overshoot of the AP decreased from 15 +/- 1 in innervated to 7 +/- 1 mV in 6-day denervated muscles. Likewise, the maximum rate of rise (+dV/dt), an expression of the inward Na(+) current, fell from 305 +/- 14 in innervated to 188 +/- 18 V.s(-1) in 6-day denervated muscles. The estimated 6-day denervated/innervated ratio of peak Na(+) conductance (g(Na)) was 0.67. The changes in AP parameters promoted by denervation were substantially reduced when both innervated and denervated fibers were hyperpolarized to -90 mV. These results suggest that the depolarization, mainly due to the increase in P(Na) /P(K) ratio, increases Na(+) inactivation and consequently reduces peak g(Na), in spite of the absolute increment in resting TTX-sensitive P(Na). This, in addition to the moderate reduction in the inward driving force on Na(+), decreases the inward Na(+) current and the extra J(i)(Na) per AP.

Action Potentials↗
PubMed2001

Caffeine-induced depolarization in amphibian skeletal muscle fibres: role of Na+/Ca2+ exchange and K+ release.

Caffeine (4 mM) produces a depolarization of about 10 mV in frog muscle fibres (Leptodactylus ocellatus). The aim of this work was to study the mechanisms of this effect. An approximately threefold rise in membrane resistance [Cl--free (SO(4)2-) medium] substantially increased, and both Na+-free medium and Ni2+ (5 mM) reduced, the caffeine-induced depolarization. In voltage-clamped (-60 mV) short fibres from lumbricalis muscle of the toad (Buffo arenarum), caffeine generated an inward current of 4.13 +/- 0.48 microA cm(-2). This caffeine-induced current was reduced by 60% in Na+-free medium, 44% in the presence of 5 mM amiloride and 48% by 5 mM Ni2+, suggesting that the activation of the Na+-Ca2+ exchanger in its forward mode may play a role in the observed electrical effects of the drug. Caffeine also produced a marked release of K+. Net K+ efflux increased from 3.5 +/- 0.2 (control) to 22.1 +/- 2.3 pmol s(-1) cm(-2) (caffeine). It is shown that in the presence of the drug, [K+] in the lumen of the T tubules may well increase to levels which could produce, in part, both the observed depolarization and the caffeine-induced current under voltage clamp conditions. The caffeine-induced K+ efflux was not reduced by 5 mM Ni2+. At a holding potential of 30 mV the caffeine-induced current was reversed (outward) and roughly halved by 5 mM Ni2+. The Ni2+-sensitive fraction of the caffeine-induced current, assumed to represent the Na+-Ca2+ exchanger current, had an estimated reversal potential close to 12 mV ([Na+]o = 115 mM; [Ca2+]o = 1 mM). In conclusion, the depolarizing effect of caffeine described here would be produced by two mechanisms: (a) an inward current generated by the activation of the Na+-Ca2+ exchanger in its forward mode, and (b) the rise of the external [K+] in restricted spaces like the T tubules.

Amiloride↗
PubMed2000

Chloride channels in toad skeletal muscle fibers.

Chloride currents were measured in short lumbricalis fibers of toads (Bufo arenarum) with voltage and patch clamp techniques. For the availability of chloride currents we applied a double-pulse technique in voltage-clamped fibers. When the test pulse was preceded by a positive prepulse, the initial current was larger than with a negative prepulse and exhibited a different rate of decline to its steady-state value. At the single-channel level we found that in most of the experiments with symmetrical 110 mM NaCl solutions, two levels of conductance, 20 ("small channel") and 360 pS ("maxi channel"), occurred with the highest probabilities. The openings of the maxi channels were more frequent at potentials close to 0 mV, whereas for the small channels the openings were at negative potentials. In contrast with the results with the macroscopic currents, a change of 2 orders of magnitude in the pH, from 7.3 to 5, had only minor effects on the channels' conductance. As with some other anion channels, the selectivity of the channels described here is low, the p(Cl)/p(Na) ratio being 1.9 and 3.7 for the small and maxi Cl(-) channels, respectively. The behavior of these Cl(-) channels with a relative high Na(+) permeability could contribute to the relatively low resting membrane potential of the lumbricalis fibers measured in the standard 110 mM NaCl solution.

Animals↗
PubMed2000

[Past and present of Medicina (Buenos Aires)].

To celebrate the 60th anniversary of Medicina (Buenos Aires) an International Symposium was held at the National Academy of Medicine of Buenos Aires on the 6-7th of October 1999, under the title of Clinical investigation in the next millennium. This meeting was a success as evidenced by the 376 registered attendants. Sixty years of uninterrupted publication is an uncommon feat in our midst and this could be achieved on the basis of a number of factors which include, the initiative of those who founded the journal, the unfailing motivation and dedication of the Editorial Board and primarily the authors who have trusted us with their manuscripts. Of the many important papers published, we have selected a few which proved to be milestones in the development of Argentine biomedicine. It is to be hoped that the future will bring an increase in our impact index through more and even better papers eventually reflecting the authentic scientific value of our country.

Argentina↗
PubMed1999

Effects of DIDS, a disulfonic stilbene derivative, on chloride movements in toad skeletal muscles.

In order to investigate the characteristics of the movement of Cl- ions in toad skeletal muscles we decided to study the relative membrane permeabilities of chloride and nitrate and the effects of DIDS (4,4'-diisothyocyanatostilbene-2,2'-disulphonate) upon the hyperpolarizations produced in muscle fibers when chloride or nitrate ions rapidly replace impermeant sulphate ions in the external solution. For experiments where membrane potential changes were recorded in response to sudden changes in extracellular solutions, small bundles from the semitendinosus muscles were used. We showed that DIDS reduced in a reversible manner the Cl- permeability (pCl) in toad skeletal muscle fibers. The results supporting this conclusion were the following. First, a diminished hyperpolarization in response to a sudden exposure of the fibers to a solution containing Cl-. In these experiments DIDS reduced the pCl/pK ratio to 5.5 from a control value of 12. Second, a smaller transient of the resting potential when [Cl]o was changed from 120 to 30 mM and vice versa.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Blockade of the inward rectifier potassium currents by zinc and nickel ions in voltage-clamped toad muscles.

The inward rectifier is one of the voltage-sensitive K+ channels present in several tissues: Its conductance increases under hyperpolarization and decreases with depolarization. In this work we studied the effects of Zn2+ and Ni2+ (5-30 mM) on the macroscopic K+ current through the inward rectifier system. The experiments were performed in the short muscle fibers of the lumbricalis muscle of toads with a two-microelectrode voltage clamp technique. The fibers were equilibrated in a control solution containing 68 mM K2SO4 and then exposed to Zn2+ or Ni2+. We found that both cations reduced in a reversible manner the current carried by K+ ions, and this reduction was prevented by decreasing the external pH of the solution (pH 5). The blockade of current was slightly dependent on the membrane potential and time independent. Two mechanisms may be involved in the blocking action of these cations: Zn2+ and Ni2+ may either be blocking the pore of the channels or acting at a regulatory binding site on the extracellular surface in an unspecified manner.

Animals↗
PubMed1997

[Ionic-channel diseases].

This review illustrates several hereditary diseases caused by mutations in genes which encode various ion channels activated by voltage or neurotransmitters. Many physiological processes depend upon the proper functioning of plasma membrane ion channels and this is most apparent in absorptive and secretory epithelia, and in electrically excitable tissues such as nerve and muscle. By combining the information from electrophysiological recordings with molecular biological techniques, further insight can be gained into the gene expression and protein structure of ionic channels. This combination has resulted in a structure-function analysis revealing the molecular substructures of the ionic channels responsible for the processes of permeation and selectivity of activation and inactivation and different types of block. Using molecular biologic tools, these abnormal channels can be identified and their molecular defects defined. Advances in these areas now provide the basis for a rational approach to the classification and treatment of these disorders of membrane excitation.

Genetic Diseases, Inborn↗
PubMed1996

Chloride current in toad skeletal muscle and its modification by the histidine-modifying reagent diethylpyrocarbonate.

Cl- currents were measured in short fibres in the toad lumbricalis muscle with a two-microelectrode voltage clamp. Membrane Cl- conductance increased markedly when external pH was raised. At pH 7 or higher, the Cl- current fell during a hyperpolarizing voltage pulse and the rate of inactivation was directly proportional to the voltage change. The histidinemodifying reagent diethylpyrocarbonate (DEPC, 1 mM) which carbethoxylates histidil residues in proteins, suppressed the inactivation of Cl- currents at pH 7.5. On the other hand, no apparent changes in the kinetics of the currents at pH 5 were seen. No3- currents, which are independent of the extracellular pH and time, were not affected by DEPC. Our results support the notion that the inactivation of Cl- currents at pH 7.5 represents a membrane permeability change and that DEPC interferes with this process. Protonation of histidine groups associated with Cl- channels may be the controlling reaction for the pH -dependent Cl- response.

Animals↗
PubMed1996

Chloride currents in skeletal muscles of Bufo arenarum.

C1- currents (ICl) were measured in short fibers (1-2 mm) from the lumbricalis muscle of toads (Bufo arenarum) with two microelectrodes (15 degrees C). Initially the fibers were equilibrated in a high (K+)-containing solution: (mM) K2SO4 68; Na2SO4 20; KCl 60; CaSO4 8; MgSO4 1; HEPES 2.5. Constant pulses were applied when all the external K+ was replaced by Cs+: Cs2SO4 68; Na2SO4 20; CsCl 60; CaSO4 8; HEPES 2.5 (pH 7.5). Under these conditions about 80-90% of the current is carried by Cl-. The current-voltage relation is almost linear implying constant conductance and hence voltage-independent permeability. The voltage dependence of the net C1- current could be fitted by constant field equation with a PCl of 3.3 x 10-6 cm/sec. In a separate group of experiments a two-pulse technique was used to estimate the availability and the inactivation of the initial ICl during a test pulse. After returning the potential to the holding potential for various times, test pulses of the same amplitude and duration of the prepulses were applied. The initial current during the test pulse was 70% of the initial current during the prepulse and the recovery was complete in less than 300 msec with a linear relationship between the current during the test pulse and the amplitude of the preceding prepulse. When the test pulses were preceded by a positive prepulse, the initial current for any given test pulse was larger than with a negative prepulse. If we assumed that the initial current during the test pulse is a measure of the number of channels open at the end of the prepulse, these results suggest that hyperpolarizing pulses inactivate and depolarizing prepulses activate the ICl.

Animals↗