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Biomedical subjects

G H Pollack

Publications and source records attributed to G H Pollack.

At least 73 records · Page 4Linked to original sources
PubMed1985

Threshold effects of acetylcholine on primary pacemaker cells of the rabbit sino-atrial node.

Leading or primary pacemaker cells located within the rabbit sino-atrial node have been identified by using electrophysiological and pharmacological techniques. Stable intracellular recordings lasting 20-30 min from cells within the s.a. node reveal three distinct patterns of spontaneous intracellular responses: (i) leading or primary pacing; (ii) follower or subsidiary pacing; and (iii) 'anomalous' pacemaker discharge. Our main objective was to measure the first detectable effect, or effects, of acetylcholine on the spontaneous intracellular electrical activity in mammalian primary pacemaker cells. Trains of brief 'field' stimuli were applied to evoke transmitter release from endogenous nerve varicosities. Systematic variations in the amplitude and duration of each stimulus, and in the train length; in conjunction with application of beta blockers (l-pindolol (10(-6) M); l-propranolol, (2 X 10(-7) M)) yielded small and transient, but very consistent negative chronotropic effects. These electrophysiological changes were blocked by atropine (1 X 10(-7) M) and were mimicked by bath application of low doses of acetylcholine (10(-7)-10(-6) M) or muscarine chloride (10(-8)-10(-7) M). In primary cells the first, or threshold effect of vagal excitation is a decrease in the slope of the pacemaker potential, without a detectable (less than 2 m V) hyperpolarization or change in action potential duration. A reduction in the dV/dtmax of the initial depolarization is also quite consistently observed. Application of longer stimulus trains yield the classical hyperpolarizing response, which is often assumed to be the major electrophysiological correlate of the negative chronotropic effect. These data provide a detailed electrophysiological description of the 'physiological' effects of the vagus nerve excitation on primary or leading pacemaker cells of the mammalian s.-a. node. A plausible explanation for the absence of hyperpolarization is suggested; and a working hypothesis is presented for the changes in ionic current or currents, that underlie this negative chronotropic effect.

Acetylcholine↗
PubMed1985

Stepwise shortening in unstimulated frog skeletal muscle fibres.

We investigated the dynamics of sarcomere length change during imposed stretches and releases of unstimulated single fibres of frog skeletal muscle. Three independent methods were used: an on-line method in which sarcomere length is computed from the striation pattern; laser diffraction; and a segment length tracking device. During steady ramp releases and stretches, both sarcomere and segment length changes occurred in stepwise fashion; i.e. periods of pause were interspersed between periods of rapid shortening. The above result indicates that activation of the fibre is not required to elicit stepwise length changes. Increasing the ramp velocity caused the steps to increase in size and the pauses to decrease in duration. Ramp releases and stretches were imposed at each of several initial sarcomere lengths up to 4.0 microns. Stepwise length changes were observed at all lengths, and their size was independent of initial sarcomere length. The observation of stepwise length changes beyond overlap indicates that the underlying mechanism probably does not lie in synchronous action of cross-bridges; an alternative hypothesis is advanced.

Animals↗
PubMed1984

Sarcomere length changes in single frog muscle fibres during tetani at long sarcomere lengths.

Laser diffraction and photomicrography have been used to monitor sarcomere length changes in single muscle fibres of the frog, at long sarcomere lengths, during fixed end tetani. In the central 90% of all fibres, changes in sarcomere length were consistently less than 0.25 micron. Sarcomere length showed an initial rapid change, followed by a progressively slower increase, which persisted throughout a 4s tetanus. Sarcomere length in the terminal 200-400 microns segment at each end of a fibre decreased rapidly by up to 1 micron in the first second of a tetanus. This shortening was accompanied by a marked increase in disorder of the striation pattern. Maximum isometric tensions in fixed end tetani were much greater than those predicted by crossbridge theory over the entire range of sarcomere lengths studied. An analysis of the intersarcomere dynamics suggests that this extra tension may be explained by known phenomena on the basis of a progressive increase in sarcomere length dispersion along the fibre.

Animals↗
PubMed1984

Stepwise shortening: evidence and implications.

The observation that sarcomeres shorten in steps has proved controversial. On the one hand, the phenomenon implies that the contractile process cannot be based on a molecular mechanism that behaves in a random manner: The fact that the steps and pauses characterize the kinetics of large volumes of tissue implies that the elements comprising such volumes must stop and pause synchronously. On the other hand, since current contractile models do not anticipate synchronized behavior, there has been considerable speculation that the phenomenon might not be a genuine feature of contraction, but an instrument-based artifact. We present here a review of observations made with four methods that have been brought to bear on the question. All four show discrete, synchronized contractile behavior. The observation of steps with multiple independent methods implies either that each technique harbors its own " gremlin " that generates spurious steps and pauses of a similar nature, or that the phenomenon is genuine. Finally, some consistent properties of the distribution of step size are considered with respect to possible molecular models.

Animals↗
PubMed1983

Quantized nature of sarcomere shortening steps.

A new technique providing real-time high-speed measurements of sarcomere length from on-line analysis of the striation image has been developed. This method of measurement is not susceptible to the problems of interpretation encountered in laser diffraction. Sarcomere shortening patterns were obtained, using this method, from single toe fibres of Rana pipiens, and stepwise phenomena similar to those previously reported from laser diffraction were observed. The distribution of step size showed several peaks, the most prominent corresponding to 5.7 nm per half sarcomere.

Animals↗
PubMed1983

Muscle contraction generates discrete sound bursts.

Isolated frog sartorius muscles were stimulated to shorten under lightly loaded conditions. A piezoelectric transducer was placed alongside the muscle to record sounds generated during contraction. Shortening was accompanied by the generation of a series of discrete sound bursts. The bursts were found to be moderately repeatable among successive contractions; 44% repeated from contraction to contraction. The duration of each sound burst was on the order of 400 mus, and the temperature dependence of the interval between successive bursts had a Q10 of approximately 2. Sound intensity was variable: average acoustic power ranged from 0.05-0.4 mW/g, or approximately 1% of the heat generated during contraction. The generation of discrete bursts of sound during contraction, rather than continuous sound, implies that contractile behavior may be discontinuous.

Animals↗
PubMed1982

Discrete sarcomere length distribution in skeletal muscle.

We analyzed the microstructure in the first-order laser diffraction line from both resting and tetanically contracting single twitch fibers from frog anterior tibial muscle to see if the distribution of sarcomere lengths is continuous or discrete. Measuring the distance between adjacent microstructural elements lying parallel, we plotted a histogram of the corresponding differences of sarcomere length. The histograms obtained both from resting and contracting fibers had a prominent peak at approximately 12-14 nm. The result suggests that the sarcomere length distribution may be discrete with unit separation of approximately 12-14-nm sarcomere length.

Animals↗
PubMed1982

The force-velocity relation and stepwise shortening in cardiac muscle.

A series of experiments was carried out to determine the effects of load variation on the character of stepwise shortening. We imposed afterloaded isotonic contractions on rat ventricular trabeculae, and measured the effect of load on pause duration, i.e., on the duration of the periods during which there was no sarcomere shortening. Sarcomere lengths were measured by optical diffraction. Increases of load brought about increases of pause duration; the relation was linear. The relation did not appear to depend on time during contraction, but did depend on sarcomere length: for a given load, pauses were longer at shorter sarcomere lengths. In a supplementary protocol in which we measured the dynamics of the central segment of the muscle during muscle isometric contraction, we found that the velocity of sarcomere shortening during the shortening step was approximately independent of load. These results provide a framework for interpretation of muscle force-velocity relations: diminished velocity at high load may be the result of increased pause durations.

Animals↗
PubMed1981

Stepwise sarcomere shortening: analysis by high-speed cinemicrography.

Sarcomere shortening in striated muscle appears to follow a regionally synchronized staircase-like time course not anticipated in some cross-bridge models. The visualization method used has been criticized as subject to Bragg diffraction effects. Two independent optical methods were used to visualize a muscle during contraction; agreement between the stepwise behavior observed with the two methods suggests that the phenomenon is genuine.

Animals↗
PubMed1981

The effect of sarcomere non-uniformity on the sarcomere length-tension relationship of skinned fibers.

It has proved difficult to activate skinned muscle fibers to produce high tension (3 kg/cm2 level) without loss of clear striations. A new method was developed which permits high tension production in skinned muscle fibers while retaining clear striations. Clear striations allow reliable measurement of the sarcomere lengths during contraction by microscopy and diffractometry. The method is to increase the Ca++ concentration of the bathing solution very gradually over a time period of 5 to 10 minutes. Once the skinned fiber is conditioned by this slow activation, subsequent contractions can be elicited by ordinary quick activations without loss of striations. When the experiments are carried out with careful controls for the uniformity of the sarcomere length distribution along the entire length of the fiber, contractions are highly repeatable. Using the new method and stringent quality control of fibers, the sarcomere length-isometric tension relationship of skinned rabbit soleus fibers was obtained. The results differ from those previously obtained by conventional activation methods in that tension increases with sarcomere length not only at low (pCa = 5.8), but also at high (pCa = 5.2), calcium concentration.

Animals↗
PubMed1978

The sarcomere length-tension relation in skeletal muscle.

Tension development during isometric tetani in single fibers of frog semitendinosus muscle occurs in three phases: (a) in initial fast-rise phase; (b) a slow-rise phase; and (c) a plateau, which lasts greater than 10 s. The slow-rise phase has previously been assumed to rise out of a progressive increase of sarcomere length dispersion along the fiber (Gordon et al. 1966. J. Physiol. [Lond.]. 184:143--169;184:170--192). Consequently, the "true" tetanic tension has been considered to be the one existing before the onset of the slow-rise phase; this is obtained by extrapolating the slowly rising tension back to the start of the tetanus. In the study by Gordon et al. (1966. J. Physiol. [Lond.] 184:170--192), as well as in the present study, the relation between this extrapolated tension and sarcomere length gave the familiar linear descending limb of the length-tension relation. We tested the assumption that the slow rise of tension was due to a progressive increase in sarcomere length dispersion. During the fast rise, the slow rise, and the plateau of tension, the sarcomere length dispersion at any area along the muscle was less than 4% of the average sarcomere length. Therefore, a progressive increase of sarcomere length dispersion during contraction appears unable to account for the slow rise of tetanic tension. A sarcomere length-tension relation was constructed from the levels of tension and sarcomere length measured during the plateau. Tension was independent of sarcomere length between 1.9 and 2.6 microgram, and declined to 50% maximal at 3.4 microgram. This result is difficult to reconcile with the cross-bridge model of force generation.

Animals↗