Locking,intermittency, and bifurcations in a periodically driven pacemaker neuron: Poincaré maps and biological implications

Slowly adapting stretch receptor (SAO) pacemaker neurons, driven with periodic tugs, were analyzed by way of Poincaré mappings (Appendix). Two behaviors were apparent, i) Intermittency characterized previously unclear situations: discharges shifted irregularly between prolonged epochs where spike phases (relative to tugs) and intervals barely changed (slid), and brief bursts with marked variations (skipped), ii) Locking was well-known: phases and intervals remained almost fixed, regardless of the initiation. Changing frequencies, map domains with locking (ordered according to spikes/tugs ratios), alternated with intermittent ones. The best fit for any experimental map was a curve, not straight but certainly unidimensional, continuous and monotonic; it varied characteristically with frequency. This suggested relations called diffeomorphisms, implying periodicity and quasi-periodicity. Outcomes, expanding previous knowledge and meaningful biologically, were i)a precise, exhaustive behavior list (including between behavior transitions) and ii)a thorough understanding or model. This, in turn, provides norms for more specific models (single-variable ones suffice), constraints upon basic mechanisms (one variable, reflecting several real ones combined, should behave as the phase), and forecasts for future experimentation (e.g., unexamined tug frequencies and amplitudes).Supported by funds from CONACYT (PCEXCNA 040539) to ODM and a donation from Trent J. Wells Inc. to JPS     

Behavior of a single neuron in a recurrent excitatory loop

A recurrent excitation loop was constructed by enabling each impulse from the slowly adapting stretch receptor organ SAO (crayfish) to trigger through an electronic circuit a brief stretch, or “tug,” of the receptor. When applied independently, each tug influenced the discharge as would an EPSP. Recurrent excitation led to characteristic discharge timings; hence, even an isolated neuron can have intrinsic mechanisms that prevent positive feedback from freezing it in an extreme non-operational state. Such timings depended critically on the “phase”, i.e., on the time elapsed between an SAO impulse and the tug. When the control discharge was stationary (because the SAO length remained invariant), phases of a few ms simply changed the pattern to one of doublets, and affected little the average rate. As the phase increased, bursts appeared, bursts and interburst intervals became more prolonged, and average rates increased. With the largest phases examined (40 ms), the discharge consisted of a slow alternation of high rate bursts, separated by long intervals. When the discharge was modulated (by 0.2/s sinusoidal length variation) with recurrent excitation, the peak-to-peak rate swing, i.e., the sensitivity, and the proportion of the cycle without afferent discharges increased, and the rate vs. length display was distorted even though remaining “loop-plus-extension.” Changes were phase-dependent: for example, loops could have a sharp high peak at one phase and be flat-topped at another. When the interspike interval variability was exaggerated (by a length jitter superimposed upon either invariant or sinusoidally varying lengths), recurrent excitation exerted fewer, weaker and somewhat different effects: e.g., it reduced the overall intensity of the invariant cases and the peak-to-peak swing in the modulated one. The precise mechanisms of these results can only be conjectured at but are likely to involve an electrogenic pump, electromechanical interactions, topographical issues, as well as their interplays. The functional implications involve, for instance, the modulation of the intensity, duration and occurrence of the bursting patterns in oscillating functions (e.g., breathing, chewing, etc.).     

Synchronization in chains of pacemaker cells by phase resetting action potential effects

Interactions between pacemaker cells in a chain were calculated according to a "phase-reset" model. It is based on effects of action potentials in the cells on the cycle lengths of neighbouring cells. These effects were defined for each cell by a latency-phase curve (LPC), giving the latency time (L) until the onset of the next action potential in that cell, as a function of the phase (phi) at which a neighbour cell fired an action potential. Neighbour cells with simultaneous action potentials did not influence each others cycle length. We investigated how stable synchronization depends on the shape of the LPC's of the pacemaker cells and on chain length. Three types of interactive behaviour were distinguished. First, anti-phase synchrony, in which neighbouring cells fired with large phase differences with respect to the synchronized period Ps. Second, asynchrony, in which the periods of the cells did not become equal and constant. Third, in-phase synchrony, in which the phase differences between the neighbouring cells were zero or much smaller than the synchronized period Ps, depending on the differences between the intrinsic periods. Asynchrony and anti-phase synchrony may be seen as cardiophysiological arrhythmias, while in-phase synchrony represents the physiological type of synchrony in the heart. In-phase synchrony appeared to be strongly favoured by LPC's, which have a no-effect (refractory) part at early phases, a lengthened latency (or phase delay) part at intermediate phases and a shortened latency (or phase advance) part at late phases in the cycle. Such LPC-shapes are commonly found in preparations of cardiac pacemaker cells. When the pacemaker cells were identical, the synchronized period Ps during in-phase synchrony was equal to their intrinsic period P*i. For different intrinsic periods, Ps was equal to the intrinsic period of the fastest cell if the LPC's contained a sufficiently long initial no-effect period at early phases and a shortened latency part at late phases. When, on the other hand, such cell chains had a linear gradient in their intrinsic periods, "action potentials" started from the fast end and traveled along the chain. The propagation of an action potential wave slowed down as it reached the slower cells. When the gradient in the intrinsic periods was too steep, only the intrinsically fast end of the chain developed synchrony.(ABSTRACT TRUNCATED AT 400 WORDS)     

Probing the circadian pacemaker of a mouse using two light pulses

In two separate sets of experiments, the phases of the locomotor activity rhythm of the nocturnal field mouse Mus booduga were probed using two light pulses (LPs). In the first set of experiments, the circadian pacemaker underlying the locomotor activity rhythm was perturbed at circadian time 14 (CT 14) using a resetting light pulse LP1 of 1000 lux intensity and 15 min duration. The phases of the resetting pacemaker were then probed at all even CTs between CT 16 and CT 14 using a PRC probing light pulse LP2 of equal strength. The "LP2 PRC" thus obtained was then compared with the single light pulse PRC in terms of the area under delay (D) and advance (A) zones of the PRCs. The time course and waveform of the two LP PRCs suggest that the LP2 PRC resembled the single LP PRC, displaced by 2 h toward the right. The LP1 PRC had smaller D compared to the single LP PRC (p = 0.007), whereas both the PRCs had A of equal magnitude (p = 0.23). This suggests that the pacemaker phase shifts rapidly after LP perturbations. In the second set of experiments, the LP1 was administered at CT 14. The phase of the pacemaker was then perturbed on day 1 (next cycle after LP1) either 2 h after activity onset (at ca. CT 14 of the transient cycle) or 8 h after activity onset (at ca. CT 20 of the transient cycle) using an LP2 of equal strength. It was observed that the steady-state phase shifts evoked by positioning an LP2, 2 h after activity onset, were positively correlated with the phase shifts observed on day 1. The steady-state phase shifts observed, when the LP2 was positioned, 8 h after activity onset, were negatively correlated with the phase shifts observed on day 1. These results suggest that the transient cycles do not mirror the state of the pacemaker oscillator.     

Lambda H-lambda T 80 hybrid study of the DNA structural gene region in lambda and phi 80 phages

Hybrids lambda H lambda T80 are formed due to recombination of the phage lambda att80 and phi 80 prophage partially deleted in the region of structural genes. Genetic structure of 22 independently isolated lambda H lambda T80 hybrids was determined by the restriction method and it was shown that recombination took place in the genes A, C, D and H. The frequencies of hybrid formation diminish from 1.10(-3) to 4.10(-5) for this gene order, which suggests that the polar divergence of nucleotide sequencies in the region of structural genes exists. It was found that formation of hybrids with recombination in the region of "weak" homology (gene H) was possible only when the region of "strong" homology was present in the deleted phi 80 prophage to initiate recombination.     

Phase-locked responses in the Limulus lateral eye. Theoretical and experimental investigation.

The 1:1 phase locking of the neural discharge to sinusoidally modulated stimuli was investigated both theoretically and experimentally. On the theoretical side, a neural encoder model, the self-inhibited leaky integrator, was considered, and the phase of the locked impulse was computed for each frequency in the locking range by imposing the condition that the "leaky integral" u(t) of the driving signal should reach the threshold for the first time one stimulus period after the preceding impulse. As u(t) can be a nonmonotonic function, this approach leads to results that sometimes differ from those reported in the literature. It turns out that the phase excursion is often much smaller than the values of about 180 degrees predicted from previous analysis. Moreover, our analysis shows a peculiar effect; the phase locking frequency range narrows when the input modulation depth increases. The theoretical predictions are then compared with phase-locked discharge patterns recorded from visual cells of the Limulus lateral eye, stimulated by sinusoidally modulated light or depolarizing current. The phases of the locked spikes at each of a number of modulation frequencies have been measured. The predictions offered by the model fit the experimental data, although there are some difficulties in determining the effective driving signal.     

R-wave synchronised atrial pacing in pediatric patients with postoperative junctional ectopic tachycardia: the atrioventricular interval investigated by computational analysis and clinical evaluation

Background

R-wave synchronised atrial pacing is an effective temporary pacing therapy in infants with postoperative junctional ectopic tachycardia. In the technique currently used, adverse short or long intervals between atrial pacing and ventricular sensing (AP–VS) may be observed during routine clinical practice.

Objectives

The aim of the study was to analyse outcomes of R-wave synchronised atrial pacing and the relationship between maximum tracking rates and AP–VS intervals.

Methods

Calculated AP–VS intervals were compared with those predicted by experienced pediatric cardiologist.

Results

A maximum tracking rate (MTR) set 10 bpm higher than the heart rate (HR) may result in undesirable short AP–VS intervals (minimum 83 ms). A MTR set 20 bpm above the HR is the hemodynamically better choice (minimum 96 ms). Effects of either setting on the AP–VS interval could not be predicted by experienced observers. In our newly proposed technique the AP–VS interval approaches 95 ms for HR > 210 bpm and 130 ms for HR < 130 bpm. The progression is linear and decreases strictly (? 0.4 ms/bpm) between the two extreme levels.

Conclusions

Adjusting the AP–VS interval in the currently used technique is complex and may imply unfavorable pacemaker settings. A new pacemaker design is advisable to allow direct control of the AP–VS interval.

     

Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart

Changes in ventricular fibrillation (VF) organization occurring after the onset of global ischemia are relevant to defibrillation and survival but remain poorly understood. We hypothesized that ischemia-specific dynamic instability of the action potential (AP) causes a loss of spatiotemporal periodicity of propagation and broadening of the electrocardiogram (ECG) frequency spectrum during VF in the ischemic myocardium. We recorded voltage-sensitive fluorescence of di-4-ANEPPS (anterior left ventricle, 35 x 35 mm, 64 x 64 pixels) and the volume-conducted ECG in six blood-perfused hearts during 10 min of VF and global ischemia. We used coefficient of variation (CV) to estimate variability of AP amplitude, AP duration, and diastolic interval (CV-APA, CV-APD, and CV-DI, respectively). We computed excitation median frequency (Median_F), spectral width of the AP and ECG (SpW-AP and SpW-ECG, respectively), wavebreak incidence (WBI), and recurrence of propagation direction (RPD). We found three distinct phases of local VF dynamics: "relatively periodic" (相似文献   

Respiration drives phase synchronization between blood pressure and RR interval following loss of cardiovagal baroreflex during vasovagal syncope

Loss of the cardiovagal baroreflex (CVB), thoracic hypovolemia, and hyperpnea contribute to the nonlinear time-dependent hemodynamic instability of vasovagal syncope. We used a nonlinear phase synchronization index (PhSI) to describe the extent of coupling between cardiorespiratory parameters, systolic blood pressure (SBP) or arterial pressure (AP), RR interval (RR), and ventilation, and a directional index (DI) measuring the direction of coupling. We also examined phase differences directly. We hypothesized that AP-RR interval PhSI would be normal during early upright tilt, indicating intact CVB, but would progressively decrease as faint approached and CVB failed. Continuous measurements of AP, RR interval, respiratory plethysomography, and end-tidal CO2 were recorded supine and during 70-degree head-up tilt in 15 control subjects and 15 fainters. Data were evaluated during five distinct times: baseline, early tilt, late tilt, faint, and recovery. During late tilt to faint, fainters exhibited a biphasic change in SBP-RR interval PhSI. Initially in fainters during late tilt, SBP-RR interval PhSI decreased (fainters, from 0.65±0.04 to 0.24±0.03 vs. control subjects, from 0.51±0.03 to 0.48±0.03; P<0.01) but then increased at the time of faint (fainters=0.80±0.03 vs. control subjects=0.42±0.04; P<0.001) coinciding with a change in phase difference from positive to negative. Starting in late tilt and continuing through faint, fainters exhibited increasing phase coupling between respiration and AP PhSI (fainters=0.54±0.06 vs. control subjects=0.27±0.03; P<0.001) and between respiration and RR interval (fainters=0.54±0.05 vs. control subjects=0.37±0.04; P<0.01). DI indicated respiratory driven AP (fainters=0.84±0.04 vs. control subjects=0.39±0.09; P<0.01) and RR interval (fainters=0.73±0.10 vs. control subjects=0.23±0.11; P<0.001) in fainters. The initial drop in the SBP-RR interval PhSI and directional change of phase difference at late tilt indicates loss of cardiovagal baroreflex. The subsequent increase in SBP-RR interval PhSI is due to a respiratory synchronization and drive on both AP and RR interval. Cardiovagal baroreflex is lost before syncope and supplanted by respiratory reflexes, producing hypotension and bradycardia.     

Electrodiffusion of ions approaching the mouth of a conducting membrane channel.

The movement of ions in the aqueous medium as they approach the mouth (radius a) of a conducting membrane channel is analyzed. Starting with the Nernst-Planck and Poisson equations, we derive a nonlinear integrodifferential equation for the electric potential, phi(r), a less than or equal to r less than infinity. The formulation allows deviations from charge neutrality and dependence of phi(r) on ion flux. A numerical solution is obtained by converting the equation to an integral equation that is solved by an iterative method for an assumed mouth potential, combined with a shooting method to adjust the mouth potential until the numerical solution agrees with an asymptotic expansion of the potential at r-a much greater than lambda (lambda = Debye length). Approximate analytic solutions are obtained by assuming charge neutrality (Läuger, 1976) and by linearizing. The linear approximation agrees with the exact solution under most physiological conditions, but the charge-neutrality solution is only valid for r much greater than lambda and thus cannot be used unless a much greater than lambda. Families of curves of ion flux vs. potential drop across the electrolyte, phi(infinity)-phi (a), and of permeant ion density at the channel mouth, n1(a), vs. flux are obtained for different values of a/lambda and S = a d phi/dr(a). If a much greater than lambda and S = O, the maximum flux (which is approached when n1(a)----0) is reduced by 50% compared to the value predicted by the charge-neutrality solution. Access resistance is shown to be a factor a/[2 (a + lambda)] times the published formula (Hille, 1968), which was derived without including deviations from charge neutrality and ion density gradients and hence does not apply when there is no counter-ion current. The results are applied to an idealized diffusion-limited channel with symmetric electrolytes. For S = O, the current/voltage curves saturate at a value dependent on a/lambda; for S greater than O, they increase linearly for large voltage.     

Single "early" action potential cause by Ni2+ ions in true pacemaker cells of the sinoatrial ring of the dace heart

Single "early" action potentials (AP) or "early" postdepolarization (EAD) were recorded in multicellular stripes working in the regimen of true pacemaker cells located in the basis of the sinoatrial valve of the dace (Leuciscus rutilus) heart after Ni2+ (0.3 mM) were added to superfused solution on the 15 th min. The standard microelectrode technique was used. The appearance of single EAD was preceded by increase of AP spike duration almost 1.5-fold due to increase of the duration of a final repolarization phase and of diastolic depolarization. EADs appeared at different levels of repolarization from -20 to -60 mV. EAD's amplitude was lower than the AP proper. The effect is reversible. Nifedipine (2 microM) decreased by 20% the AP duration to 50% repolarization in the cells of atrial type. In case the stripes were primarily subjected to nifedipine effect and then even after a long procedure of washout, the Ni2+ (0.3 mM) did not cause EADs. The hypothesis has been tested of what is the main reason of single EAD appearance in pacemaker cells under the effect of Ni2+; it is either blocking Ca release from the cell by Ni2+, or reactivation of L-type Ca-channels' conductivity. The analysis of the data obtained leads to the conclusion that 30-50% Na-Ca-exchangers block is the basic reason of single EAD appearance in pacemaker cells.     

Recurrent inhibition: Its influence upon transduction and afferent discharges in slowly-adapting stretch receptor organs

The crayfish stretch receptor organs provide the opportunity to study recurrent inhibition (RI) in pure experimental conditions. The slowly adapting organ (SAO) from the cephalothoraxabdomen joint of Procambarus darkii was isolated and its length set by anchoring one end and clamping the other with a movable forceps. Each impulse from the SAO triggered a shock to the common inhibitory fiber, after an adjustable delay called phase. Thus, RI acted upon the SAO. Under steady length conditions, the discharge rate with RI was proportional to the spontaneous discharge rate (i.e. to that without RI), and negatively correlated to the ratio of the phase to the spontaneous interspike interval. Under dynamic conditions, with the SAO submitted to under 0.3 mm length variations, sine-like with or without white noise, and periodic at 0.2, 1.0, or 3.0 cps, the effect of RI was basically the same in all conditions. While the lower rates of discharge were unchanged, the higher rates were reduced: thus the overall sensitivity of the SAO was decreased. The RI also decreased the discharge variability at the low rates; variability remained unaffected at the high rates. The general form of the response of the SAO was unaffected by RI, as indicated by displays of rate versus length, of rate versus velocity, or of change in rate versus velocity: only the widness of the loops changed. The effects of RI were compared to those of randomly arriving, Poisson-like IPSP's at the same overall rate: the latter did not exhibit the same dependence on the SAO firing rate.Supported by grants from NIH and NSF     

A model of excitatory synaptic interactions between pacemakers. Its reality,its generality,and the principles involved

This is a model of the steady-state influence of one pacemaker neuron upon another across a synapse with EPSP's. Its postulates require firstly the spontaneous regularity of both cells, whose intervals are E and N, respectively. In addition, they require a special shortening or negative delay of the interspike interval by one or more EPSP's, with a V-shaped dependence of the delay on the position or phase of the EPSP's in the interval; the minimum of the delay function corresponds to the earliest EPSP arrival phase () that triggers a spike immediately. Finally, they impose on the variables certain bounds. The model's behavior has two main features. The first is a zig-zag relationship with an overall increasing trend between the steady-state pre- and post-synaptic discharge intensities (Fig. 7). The zig-zag is formed predominantly, if not exclusively, by segments with positive slopes that are rational fractions. Passage from one such segment to others is negatively-sloped (paradoxical), involving staggered positively-sloped segments whose details are unclear for weak presynaptic discharges and discontinuities for intense discharges. The same postsynaptic intensity may result from several presynaptic ones; the maximum postsynaptic intensity may reflect refractoriness, or the earliest instants of immediate triggering. The second main feature is the locking of the discharges in an invariant forward and backward temporal relation. With at most one EPSP per postsynaptic spike, locking is always present. If the presynaptic interval E is in the closed {rN+,(r+1)N} range, locking is 1:r+1, either stable at a greater-than- phase or unstable at a smaller one; arrivals at integral multiples of N do not affect the postsynaptic intensity. If E is in {rN, rN+} (r>0), locking is at other ratios (e.g., 2:3) and less apparent. With more than one EPSP per spike, when E is below bounds that depend on the interspike interval and the point of earliest triggering, locking happens in the simple s:1 ratio (s=2,3, ...) and is stable; when E is above those bounds, there are E ranges where locking is in other ratios (e.g., 3:2) and ranges where behavior is unclear. The validity of any model is based jointly upon an a priori judgment as to whether postulates depart reasonably little from nature, and upon an a posteriori experimental comparison of modelled and real behaviors. The model's domain of applicability depends on the specific embodiment, each of the latter tolerating characteristically each departure. The present model will be evaluated in the crayfish stretch-receptor neuron (Diez-Martínez et al., in preparation). The model is applicable to any physical system that complies with its postulates, and evidence compatible with this notion is available in many disparate fields. It illustrates the modelling path to a scientific proposition, other paths being inference from experimentation, or deduction from premises acceptable at other approach levels (in this case, for example, from that of synaptic mechanisms). The periodicity postulates set this model within the category of those for oscillators. The notion of an oscillator has a far broader applicability than appears at first sight, since all physically realizable systems have some predominant output frequency, i.e., to a certain extent are oscillators.Supported by funds from the Brain Research Institute, UCLASupported by FAPESP (Sao Paulo, Brazil). Present address: Esc. Politecnica, Dee, University of Sao Paulo, Cid. Univ., CP 8174 Sao Paulo, S.P., Brazil     

Phase locking induces scale-free topologies in networks of coupled oscillators

An initial unsynchronized ensemble of networking phase oscillators is further subjected to a growing process where a set of forcing oscillators, each one of them following the dynamics of a frequency pacemaker, are added to the pristine graph. Linking rules based on dynamical criteria are followed in the attachment process to force phase locking of the network with the external pacemaker. We show that the eventual locking occurs in correspondence to the arousal of a scale-free degree distribution in the original graph.     

Prohead and DNA-gp3-dependent ATPase activity of the DNA packaging protein gp16 of bacteriophage phi 29

The ATPase activity of the DNA packaging protein gp16 (gene product 16) of bacteriophage phi 29 was studied in the completely defined in-vitro assembly system. ATP was hydrolyzed to ADP and Pi in the packaging reaction that included purified proheads, DNA-gp3 and gp16. Approximately one molecule of ATP was used in the packaging of 2 base-pairs of phi 29 DNA, or 9 X 10(3) ATP molecules per virion. The hydrolysis of ATP by gp16 was both prohead and DNA-gp3 dependent. gp16 contained both the "A-type" and the "B-type" ATP-binding consensus sequences (Walker et al., 1982) and the predicted secondary structure for ATP binding. The A-type sequence of gp16 was "basic-hydrophobic region-G-X2-G-X-G-K-S-X7-hydrophobic", and similar sequences were found in the phage DNA packaging proteins gpA of lambda, gp19 of T7 and gp17 of T4. Having both the ATP-binding and potential magnesium-binding domains, all of these proteins probably function as ATPases and may have common prohead-binding capabilities. The phi 29 protein gp3, covalently bound to the DNA, may be analogous in function to proteins gpNul of lambda and gpl of phi 21 that bind the DNA.     

Mechanism of non-tandem integration of prophage phi 80 into the chromosome of the wild-type Escherichia coli

We studied the ability of lambda, phi 80 and their hybrid lambda att80 to lysogenize homoimmune monolysogens and examined the prophage locations on the chromosome of the resulting polylysogens. We observed an effective integration of phi 80 and lambda att80, in contrast to lambda, into the host chromosome, exclusively, at the attachment sites that were not occupied by the resident prophage (nontandem). Besides, the lambda att80 (int+) prophage was observed to ensure effective nontandem integration of a homoimmune int mutant DNA. Hence, we inferred that the expression of the int gene in the phi 80 prophage is constitutive, cI-independent and results in nontandem integration of the homoimmune prophage. The validity of this inference has been supported experimentally: (i) the only lysogen that was found to contain a phi 80 tandem was highly unstable (spontaneous segregation of monolysogens occurred 6-7 times more frequently than with the lambda tandem); (ii) an int inactivating mutation stabilized the phi 80 tandem; as a result, the int mutant has the frequency of tandem integration as high as that of lambda, while no nontandem integration was observed. A hypothesis is proposed which accounts for the instability of the phi 80 tandems and explains the relation between this phenomenon and the prophage ability to integrate into secondary attachment sites in the presence of the primary (normal) one.     

Temperature acclimation modifies sinoatrial pacemaker mechanism of the rainbow trout heart

The hypothesis of pacemaker level origin of thermal compensation in heart rate was tested by recording action potentials (AP) in intact sinoatrial tissue and enzymatically isolated pacemaker cells of rainbow trout acclimated at 4 degrees C (cold) and 18 degrees C (warm). With electrophysiological recordings, the primary pacemaker was located at the base of the sinoatrial valve, where a morphologically distinct ring of tissue comprising myocytes and neural elements was found by histological examination. Intrinsic beating rate of this pacemaker was higher in cold-acclimated (46 +/- 6 APs/min) than warm-acclimated trout (38 +/- 3 APs/min; P < 0.05), and a similar difference was seen in beating rate of isolated pacemaker cells (44 +/- 6 vs. 38 +/- 6 APs/min; P < 0.05), supporting the hypothesis that thermal acclimation modifies the intrinsic pacemaker mechanism of fish heart. Inhibition of sarcoplasmic reticulum (SR) with 10 microM ryanodine and 1 microM thapsigargin did not affect heart rate in either warm- or cold-acclimated trout at 11 degrees C but reduced heart rate in warm-acclimated trout from 74 +/- 2 to 42 +/- 6 APs/min (P < 0.05) at 18 degrees C. At 11 degrees C, a half-maximal blockade of the delayed rectifier K+ current (I(Kr)) with 0.1 microM E-4031 reduced heart rate more in warm-acclimated (from 45 +/- 1 to 24 +/- 5 APs/min) than cold-acclimated trout (56 +/- 3 vs. 48 +/- 2 APs/min), whereas I(Kr) density was higher and AP duration less in cold-acclimated trout (P > 0.05). Collectively, these findings suggest that a cold-induced increase in AP discharge frequency is at least partly due to higher density of the I(Kr) in the cold-acclimated trout, whereas contribution of SR Ca2+ release to thermal compensation of heart rate is negligible.     

Recombination of bacteriophage phi X174 by the red function of bacteriophage lambda.

Recombination of bacteriophage phi X174 was effectively promoted when the Red function of lambda was supplied by either co-infection with lambda or induction of lambda lysogens. Mutations in red alpha and red beta genes of lambda abolished recombination nearly completely, whereas a mutation in gam gene reduced it only slightly. The Red-promoted recombination of phi X174 occurred in recA, recB, and polA mutants as well as in wild-type strains of Escherichia coli. It was further stimulated when phi X174 mutants were irradiated with UV light before infection.