Electrogenic hyperpolarization in canine cardiac Purkinje fibres exposed to calcium ionophores

Summary The Ca ionophores markedly enhance the increase of intracellular Ca occurring during Na-free perfusion and the hyperpolarization observed upon Na readmission may be due to rapid restoration of intracellular Na and resultant stimulation of both electrogenic sodium and calcium efflux.This work was supported by a grant-in-aid and a Senior Investigatorship from the New York Heart Association.     

The electrophysiological effects of ionophore X-537A on cardiac Purkinje fibres

Summary Using classical microelectrode techniques in canine cardiac Purkinje fibres, calcium ionophore X-537A was shown to shorten the action potential, hyperpolarizing the membrane and lowering the plateau, suggesting that intracellular calcium controls membrane permeability to potassium in this preparation.This work was supported by grant No. HL 05726 from the U.S. Public Health Service, National Heart Institute, Bethesda, Md.I thank Dr.N. Krasnow for his valuable advice in carrying out this work.     

The Na/K pump,resting potential and selective permeability in canine Purkinje fibres at physiologic and room temperatures

All mammalian cells maintain a resting potential generated by ions moving down concentration gradients. In excitable cells, the inside potential is negative relative to outside. In order to maintain this electrochemical gradient, the sodium potassium (Na/K) pump actively transports out three sodium ions for every two potassium ions it brings in. This process generates a net outward current and thus hyperpolaizes the resting potential. I employed dihydroouabain (DHO) to inhibit the Na/K pump and thus measure its contribution to the resting potential. It contributed 9.0 mV at 34°C and 3.8 mV at 25°C. The P_K/P_Na ratios were calculated at both temperatures before and after subtracting the Na/K pump contribution. These ratios also suggested a decreased contribution of the Na/K pump under hypothermia. Taken together, these results suggest that the pump contribution to the resting potential is more significant at physiologic temperatures (34°C) than at room temperature (25°C), and that estimates of selective permeability can only be accurately obtained after assessing and eliminating the Na/K pump contribution to the resting potential.     

Sodium channels in cardiac Purkinje cells

Sodium (Na+) currents are responsible for excitation and conduction in most cardiac cells, but their study has been hampered by the lack of a satisfactory method for voltage clamp. We report a new method for low resistance access to single freshly isolated canine cardiac Purkinje cells that permits good control of voltage and intracellular ionic solutions. The series resistance was usually less than 3 omega cm2, similar to that of the squid giant axon. Cardiac Na+ currents resemble those of nerve. However, Na+ current decay is multiexponential. The basis for this was further studied with cell-attached patch clamp recording of single Na+ channel properties. A prominent characteristic of the single channels was their ability to reopen after closure. There was also a long opening state that may be the basis for a small very slowly decaying Na+ current. This rare long opening state may contribute to the Na+ current during the action potential plateau.     

Na-Activated calcium efflux in rabbit vagus nerve fibres

Zusammenfassung Die vorliegenden Resultate deuten darauf hin, dass aus marklosen Nervenfasern ein passiver Austausch von intrazellulärem Kalzium gegen extrazelluläres Natrium erfolgt, und zwar mittels eines überträgersystems, das von dem für die Erregung notwendigen Na-übertragenden System verschieden ist.     

Methylation of canine cardiac myosin in culture

Summary N, N, N, trimethyllysine and an unidentified methylated amino acid which co-electrophoresed and cochromatographed with the hydrolysis product of S-adenosyl-L-methionine, occur in fetal canine cardiac myosin and are isotopically labeled in vitro with S-adenosyl-L-(methyl³H) methionine between the 10th and the 12th day of culture.     

Enhanced excitability in locust muscle fibres induced by calcium free saline

Summary The membrane of locust muscle fibres normally exhibits a graded electrical response to outward current pulses of increasing strength. On removal of Ca⁺⁺ ions from the external medium, these fibres are shown to exhibit depolarizing membrane responses of variable time course and duration. These responses are abolished in Na⁺-free solutions, and by the addition of Mn⁺⁺ ions.D.A.M. was the recipient of a Royal Society and Science Research Council European Exchange Fellowship. We thank the Centre for Overseas Pest Research, Kensington for supplying the locusts.     

Activation of the electrogenic Na-pump of cardiac muscle fibres by ACh in K-free solutions

Summary The ionic mechanism of the membrane outward current (ACh-current) of bullfrog atrium muscle, induced by acetylcholine in K-free solution, was analyzed by a voltage-clamp experiment. The results suggested that the ACh-current was induced not only by an increase in K-conductance but also by an activation of the electrogenic Na-pump.Acknowledgment. This work was supported by a grant (257037) from the Ministry of Education of Japan.     

Identification of swelling-activated Cl<Superscript>-</Superscript> current in rabbit cardiac Purkinje cells

The presence and functional role of the swelling-activated Cl^- current (I_Cl(swell)) in rabbit cardiac Purkinje cells was examined using patch-clamp methodology. Extracellular hypotonicity (210 or 135 mOsm) activated an outwardly rectifying, time-independent current with a reversal potential close to the calculated Cl^- equilibrium potential (E_Cl). The magnitude of this current was related to tonicity of the superfusate. The current was blocked by 0.5 mM 4,4-diisothiocyanostilbene-2,2-disulfonic acid (DIDS). These features are comparable to those of I_Cl(swell) found in sinoatrial nodal, atrial, and ventricular myocytes. I_Cl(swell) activation at 210 and 135 mOsm depolarized the resting membrane potential with 6 and 10 mV and shortened the action potential by 18 and 33%, respectively. DIDS partially reversed I_Cl(swell)-induced action potential changes. We conclude that I_Cl(swell) is present in Purkinje cells and its activation leads to action potential shortening and resting membrane potential depolarization, both of which can promote the development of reentrant arrhythmias.Received 20 January 2004; received after revision 17 February 2004; accepted 25 February 2004     

Activation of the electrogenic Na-pump of cardiac muscle fibres by ACh in K-free solutions.

The ionic mechanism of the membrane outward current (ACh-current) of bullfrog atrium muscle, induced by acetylcholine in K-free solution, was analyzed by a voltage-clamp experiment. The results suggested that the ACh-current was induced not only by an increase in K-conductance but also by an activation of the electrogenic Na-pump.     

Pineal N-acetyltransferase depression in rats exposed to heat

Summary Exposure of adult male rats to increased temperature of 33±1°C for 3 and 10 days brought about decreases in pineal N-acetyltransferase activity. These and previous findings of pineal HIOMT inhibition under similar conditions support the postulation of a possible thermoregulatory role for the pineal gland.     

Sodium pump: Its importance to intercellular communication in heart fibres

Summary The effect of ouabain on the electrical coupling of canine Purkinje cells was investigated. It was found that the glycoside decreases cell communication through an increase in junctional resistance, what supports the view² that the sodium pump has an important role on the control of cell communication.This work was supported by Grant No. HL-10897 from the National Heart and Lung Institute, Bethesda, Maryland; from the P.R. Heart Association and from the General Research Support Grant.     

Brain to body relationships in ontogeny of canine brain

Zusammenfassung Die Relation Gehirnmasse/Körpergewicht wurde bei 83 Hunden von Geburt bis zum Adultzustand studiert. Ein Bruch in der linearen Relation zwischen den Logarithmen Gehirngewicht und Körpergewicht trat ungefähr im Alter von vier Wochen ein (1,5 kg Körpergewicht zu 37 g Gehirngewicht). Dies betrifft einen kritischen Punkt in der Neuro-Ontogenie, was im Zusammenhang mit anderen Erscheinungen der ZNS- und Verhaltensentwicklung steht.     

Growth inhibition in mammalian cells exposed to thermal stress

Zusammenfassung Erhöhter Temperatur ausgesetzte Schweinenieren-Zellen produzieren, bei 37 °C kultiviert, Mikrokolonien. Eine Reduktion in der Wachstumsrate ist proportional zur Dauer und Intensität der Hitzebehandlung und verliert sich im Laufe der weitern Kultivierung.

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This work was supported by U.S. Public Health Service Research Grant No. GM-13692, and by an appointment as Research Professor in the Miller Institute for Basic Research in Science.     

Enhanced calcium accumulation related to increased protein phosphorylation in cardiac sarcoplasmic reticulum induced by cyclic 3′, 5′-AMP or isoproterenol

Zusammenfassung Die cAMP-abhängige Inkorporation von³²P in das sarkoplasmatische Reticulum (SR) wurde im Zusammenhang mit Ca-Akkumulation in Kontrollherzen und in Herzen 2 h nach in vivo Verabreichung von 7,5 mg/kg Isoproterenol gemessen und gezeigt, dass die Katecholamine den intrazellulären Kalziumtransport in vitro sowie in vivo über die cAMP-stimulierte und PK-abhängige Phosphorylierung einer Proteinfraktion des SR regulieren.