The rat heart demonstrates marked alterations in its responses to ouabain and increased frequencies of stimulation and in the duration of its action potential during the initial 21 days of life. At an age of 6.2 days 5 x 10" 5 M ouabain produced a 158.2% increase in dP/dt compared with a 17.2% increase at 21.1 days (P < 0.001). At 6.2 days dP/dt increased by 53.4% when the heart rate was accelerated from 30 to 90 beats/min compared with an increase of 12.2% at 21.1 days (P < 0.005). The positive glycoside and staircase responses at the younger age were virtually eliminated when the hearts were perfused with a solution containing 50% [Na + ] o and 25% [Ca 2+ ]o ([Ca 2+ ] o /[Na + ] 0 2 maintained constant). The duration of the ventricular action potential progressively decreased from 350-400 msec at birth to 100-150 msec at 21 days of life. This decrease was due to a shortening and a decrease in the potential level of the plateau phase. The prominent plateau typical of the early neonatal period was significantly diminished by perfusion with 50% [Na + ] o . The results suggest that Na + flux through a slow membrane channel plays a significant role in the positive staircase and glycoside responses of the early neonatal rat heart. As the heart matures and becomes functionally anomalous relative to other mammalian species, the slow channel progressively closes.
KEY WORDSsodium flux calcium excitation-contraction coupling slow sodium channel ouabain dP/dt action potential plateau• The adult rat heart demonstrates a number of unique physiological and pharmacological characteristics. It has an action potential of short duration with little evidence of a plateau (1) and an interval-force relationship (staircase) which is atypical in that it is dominated by a tendency for contractile strength to decrease with increasing frequency (2); moreover, the adult rat heart is particularly resistant to the action of digitalis glycosides (3, 4). The neonatal rat heart however has strikingly different characteristics with respect to all of these phenomena. The purpose of the present study was to document these characteristics over the early neonatal period. If the sequential changes related to age are interrelated, an understanding of them might provide further clues to the ionic mechanisms important in the control of the myocardial contractile response.
MethodsSprague-Dawley rats were used for all of these studies. The standard perfusion medium had the following millimolar composition: NaCl 142, KC1 4, MgCl 2 1.0, CaCl 2 1.0, and glucose 5.56. When it was buffered with 3 mM HEPES (N-2-hydroxyethylpiperazine-N'-2-ethane sulfonic acid), the perfusate was equilibrated with 100% O 2 ; when it was buffered with 12 mM NaHC0 3 , the NaCl content was lowered to 130 mM and the perfusate was equilibrated with 98% O 2 -2% CO 2 . The standard solution was modified to give a "low Na + -low Ca 2+ " solution by replacing 71 mmoles NaCl/liter with 71 mmoles choline chloride/liter and decreasing the Ca 2+ concentration to 0.25 mM; th...
SUMMARY1. A technique is described whereby (i) quick stretches and releases of controlled velocity, amplitude and time of onset can be applied to muscle.(ii) Releases from isometric to isotonic contraction can be performed at controlled delays relative to the stimulus, and displayed on a delayed expanded oscilloscope sweep. An isotonic lever system with an equivalent mass of 12-8 mg is described.2. Quick stretch of rabbit or cat papillary muscle after excitation does not result in a level of tension equal to or greater than normal peak isometric tension appropriate to the stretched length. Stretches applied during the first half of the rising phase of tension development give responses nearly identical to the same stretches applied before the stimulus (indicating that Starling's Law of the heart holds until this time). Stretches applied in the later phase oftension development or during relaxation resuIt in diminished peak isometric tensions or accelerated relaxation.3. The rate of tension development following quick releases of isometrically contracting muscle to zero tension is not maximal until the releases are made 150-200 msec after excitation.
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