Per Arlock

Temperature effects on the Na and Ca currents in rat and hedgehog ventricular muscle

Cardiac transmembrane potentials and Na and Ca currents were recorded at different temperatures in rat and hedgehog ventricular muscle. At 35 degrees C in both species resting potential was about -80 mV and upstroke velocity (Vmax) of the action potential above 100 V/s. The shape of the action potential in hedgehog ventricular cells at 35 degrees C was similar to that in the rat showing a fast repolarization phase. When temperature was decreased, the membrane resting potential depolarized and action potential amplitude and Vmax declined. In rat ventricular cells at 10 degrees C, the resting potential was about -40 to -50 mV and Vmax was reduced to about 5 V/s. In hedgehog ventricular cells, however, the transmembrane potentials and Vmax were better maintained at low temperature. Phase 3 of the action potential was markedly prolonged below 20 degrees C in hedgehog but not in rat ventricular cells. When temperature was decreased to 10 degrees C the availability curve of the Na current shifted toward more negative potentials and ICa.peak declined in rat ventricular cells. In hedgehog cardiac preparations, the Na current was less influenced by the cooling and ICa.peak did not change very much at low temperatures. A transient inward current usually considered to induce cardiac arrhythmias could be recorded in rat ventricular cells below 20 degrees C but not in hedgehog preparations. These features of hedgehog cardiac membranes may contribute to the cold tolerance and the resistance to ventricular fibrillation during the hypothermia in mammalian hibernators.

Cardiac electrophysiology of four neuroleptics: melperone, haloperidol, thioridazine and chlorpromazine.

SummaryThe effect of melperone on the isolated guinea-pig papillary muscle were compared with those of three other neuroleptics-haloperidol, thioridazine and chlorpromazine. At 10−6 M only melperone prolonged the effective refractory period without reducing contractility. With melperone in the concentration 10−5 M and less, no further changes other than a homogeneous prolongation of the action potential were found.Haloperidol at 10−6 M caused a prolongation of the action potential, a flattening of the repolarization phase and a 40% decrease in contractile force. At 10−5 M haloperidol reduced the resting potential (RP), the action potential amplitude (AP), the maximum upstroke velocity (MUV) of the action potential and the contractile force.Thioridazine at 10−6 M reduced MUV and the contractile force. At 10−5 M thioridazine decreased the overshoot and a very pronounced decrease in MUV was registered. A flattening in the repolarization phase was seen from 10−6M.Chlorpromazine at 10−6 M reduced MUV, contractile force and caused a flattening of the repolarization phase. At 10−5 M chlorpromazine decreased the overshoot and the RP and caused a very pronounced decrease in the MUV.Thus, melperone differed from the other compounds in the ability to induce homogeneous prolongations of the action potential and the effective refractory period without affecting the contractility. (Antiarrhythmic activity of type III of Vaughan-Williams, 1970.)

Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction by an intracellular calcium-dependent mechanism

The potentiating effect of neuropeptide Y (NPY) was examined by testing the influence of putative inhibitors of calcium entry on the NPY-enhanced contractile response to noradrenaline in the guinea pig uterine artery. In order to examine the involvement of voltage sensitive calcium entry mechanisms we recorded the effect of noradrenaline and NPY on the membrane potential. NPY (100-300 nM) enhanced noradrenaline-evoked vasoconstriction. The potentiation by NPY was most prominent in low noradrenaline concentrations (30-300 nM) and the pD10 (-log molar concentration of agonist eliciting 10% of maximum contraction) value was increased from 6.43 +/- 0.07 to 6.97 +/- 0.11 (P < 0.001, n = 6). Inhibition of extracellular calcium influx shifted concentration-dependently to the right the concentration-response curve for noradrenaline but potentiation by NPY still remained. The intracellular calcium chelator quin-2 AM selectively abolished the NPY-induced enhancement of the contractile response to noradrenaline. In contrast, quin-2 AM (10-30 microM) had no inhibitory effect on the contractile response to noradrenaline per se. It is suggested that NPY initiates an intracellular calcium-sensitive mechanism which increase alpha-adrenoceptor sensitivity. This results in a significant increase of sarcoplasmic calcium and stronger contractile responses to noradrenaline.

Neuropeptide Y in cerebrovascular function: comparison of membrane potential changes and vasomotor responses evoked by NPY and other vasoconstrictors in the guinea pig basilar artery

The membrane depolarization and vasomotor response evoked by NPY and other vasoconstrictors were compared in guinea pig basilar artery. Concentrations below the pD2 value of amines and PGF2 alpha induced contractions without significant membrane depolarization, while higher agonist concentrations depolarized the membrane slightly. Potassium-induced contractions were paralleled by strong depolarization. NPY evoked a slow depolarization which correlated to vasoconstriction over a wide concentration range. The mechanism of activation did not appear to involve the endothelium. The results suggest that NPY induces prolonged cerebrovascular smooth muscle tone by evoking longlasting depolarization, at least partly in conjunction with activation of voltage-operated calcium channels.

The negative inotropic effect of esmolol on isolated cardiac muscle.

Objective. Esmolol is an ultra-short-term acting beta adrenergic blocker for intravenous use. The most common side effect is hypotension, which is often manageable by careful titration of the dose. We speculated whether esmolol had a direct negative inotropic effect on the cardiac muscle. Design. Papillary muscles and trabeculae were excised from guinea pig and pig hearts. Force production was recorded together with action potentials. Membrane currents were recorded in isolated myocytes. The effects of two concentrations of esmolol were tested (55 and 110 µmol/L). Results. Esmolol reduced action potential duration and plateau voltage, and decreased force production of isolated cardiac muscle. Voltage-clamp experiments from a holding potential of −40 mV and a step change to 0 mV showed a reduction in the inward current due to esmolol. Conclusion. Apart from being a beta adrenergic blocker esmolol also exerts a direct negative inotropic effect on cardiac muscle due to its inhibition of the calcium current during the action potential.

Effects of dopamine on porcine myocardial action potentials and contractions at 37 degrees C and 32 degrees C

Background: Little information exists on the effects of drugs with cardiovascular action in hypothermia, and some findings have indicated paradoxic effects of dopamine in this setting. As we have not found any data on the electrophysiologic and contractile effects of dopamine on the heart in hypothermia, we decided to study this in pig myocardium, since pigs have a cardiovascular system more similar to that of humans than other animals.

Electrical activity and mechanical response in the systemic heart and the portal vein heart of Myxine glutinosa

Abstract 1. 1. Electrical activity was registered in situ with a bipolar lead directly of the systemic heart cavities and the portal vein heart cavities of the hagfish, Myxine glutinosa. 2. 2. Electrical activity was also registered intracellulary with the aid of microelectrodes in the atrium and ventricle of the systemic heart and in the portal vein heart. 3. 3. The mechanical response was registered at the same time as the electrical activity. 4. 4. The different deflection of the electrocardiograms were identified. 5. 5. Absolute values were determined for various transmembrane action potentials. 6. 6. The time relationships between the electrical activity and the mechanical response were analyzed.

Intercellular voltage gradient between oocyte and nurse cell in a polychaete.

In the polychaete Ophryotrocha labronica the oocyte is supported during vitellogenesis by a single nurse cell, which is cytoplasmically contiguous with the oocyte through an intercellular bridge. Our electrical measurements demonstrate a marked potential difference (22-32 mV) between the oocyte and the nurse cell in mid-vitellogenesis, suggesting an electrophoretically caused migration of nurse cell constituents into the oocyte. Possibly this potential gradient helps to create a developmental prepattern in the oocyte, a role postulated for similar gradients within the oocyte-nurse cell complex of the Cecropia moth.

The influence of the surface electrogram on the rising phase of the mammalian cardiac action potential

Abstract1.When guinea pig cardiac tissue is stimulated, the rising phase of the action potential is influenced by the shape of the concomitant local surface electrogram. This, in turn, depends on the direction of the wave of excitation passing the recording microelectrode.2.A symmetrical biphasic surface electrogram yields sigmoid upstrokes with maximum upstroke velocity (Vmax) lower than when it is either zero or uniphasic and negative.3.When the main direction of the depolarization wave in guinea pig ventricular myocardium is receding from the recording microelectrode, giving rise to negative uniphasic extracellular potentials, a notch might distort the registration of the rising phase of the action potential.4.When the main direction of the depolarization wave is approaching the recording microelectrode, giving rise to positive uniphasic extracellular potentials,Vmax is transferred to less negative membrane potentials.5.The extracellular surface electrogram influences the overshoot of the action potentials of the normal atrial and depressed (D-600) ventricular myocardium and is changed, depending on how the wave of excitation passes the recording microelectrode.

Effects of db-cAMP on the transmembrane potentials of cultured human glioma cells.

Abstract Human glioma cells (138MG) had transmembrane potentials around −35 mV. The potentials appeared to be independent of cell density, cell morphology and presence or absence of serum in the culture medium. Dibutyryl cyclic AMP (db-cAMP) (1 mM) induced morphological alterations and increased the potentials of various cellular phenotypes by 9–14 mV, whereas sodium butyrate (1 mM) lacked effect. The db-cAMP-induced increase was observed after 2 h incubation and persisted for at least 48 h. Cycloheximide (10 μg/ml) had no effect on the db-cAMP-induced increase in transmembrane potential. The 138 MG transmembrane potential was potassium dependent.