Rapid Recovery Phase Research Articles

Effects of Bepridil on Atrial Electrical Remodeling in Short-Term Rapid Pacing

Introduction: Bepridil is a multi-ion channel blocker similar to amiodarone. Recent clinical studies have indicated that bepridil shows a favorable efficacy for the treatment of atrial fibrillation (AF). The purpose of this study is to evaluate the effectiveness of bepridil for electrical remodeling induced by rapid atrial stimulation particularly in the acute-phase. Methods and Results: We studied 18 pigs subjected to right atrial appendage rapid pacing at 500 beats/min for 3 hours that were randomly assigned to the absence or presence of bepridil administration for 14 days. They were divided into 2 groups, an atrial pacing only group (PG; n = 10) and an atrial pacing plus bepridil group (PBG; n = 8). We measured the effective refractory period (ERP) at the right atrial free wall (RAFW), the right atrial appendage (RAA) and the left atrial free wall (LAFW), as well as the monophasic action potential duration at 90% (MAPD90) in RAA during the rapid pacing phase and recovery phase. In the PG, the ERP decreased gradually at all atrial sites during the 3 hour phase of rapid pacing. In contrast, the shortening of the ERP was suppressed significantly at the RAFW and LAFW in the PBG. The MAPD90 was also shortened by rapid atrial pacing in the PG. This shortening was suppressed significantly in the PBG. We evaluated the effect of bepridil on the inducibility of AF during all time spans. The mean number of AF occurrences in the PBG was significantly fewer than in the PG. (2:1 ± 2:4 vs. 8:5 ± 7:0, p < 0:05) Conclusions: Bepridil prevented the shortening of the ERP and MAPD90 induced by rapid atrial pacing in the acute phase. The results of this study might explain the efficacy of bepridil for preventing the recurrence of paroxysmal AF.

Global and local attention in the attentional blink

This study examines the attentional blink (AB) under conditions where attention was directed either to the overall (global) or to the component (local) form of compound Navon letters. Forty-five adult participants were presented RSVP sequences of compound letter stimuli and were asked to identify the prescribed attentional aspect of a red target letter (T1) and to detect the presence of a second item (T2 = letter X), again of specified global or local aspect. Trials were presented at either four or six letter forms per second (f/s). We report that the AB estimated from the mean performance across participants is much longer (1.5-2.5 s) than that reported previously with single letter RSVP (200-500 ms). A lag-1 sparing effect was not observed when data were filtered for correct identification of T1. Characteristic rapid (initial) and slower (later) recovery phases suggested the use of a bilinear ("knee") recovery model, possibly identifying a novel slow recovery mechanism for the AB when its duration is sufficiently long. However, it is proposed that the duration of the AB should be analyzed by estimation of each individual's AB prior to group analysis. Analysis of individual bilinear fits to the data shows a significant effect of attentional condition for the 4 f/s data, with more rapid recovery for Global-Global (GG) than Local-Local (LL) target conditions, consistent with the global precedence hypothesis. While the 6 f/s data did not demonstrate such differences between attentional conditions, it was at the expense of T1 identification performance with significantly poorer T1 identification for the LL cf GG conditions. Individual fits also demonstrate that the later slow recovery phase seen in the population mean data is clearly a result of pooling of the data from individuals reaching ceiling performance in recovery at different times. Analysis of the trials in which T1 was incorrectly identified yielded an attentional blink for T2 with delayed recovery and a manifest lag-1 sparing effect. This suggests, in the framework of the two stage model, that the duration of gate opening for target recognition requires sufficient certainty of recognition prior to closure, rather than being a fixed, process-related time.

Revival of Tourism in Sri Lanka following the December 2004 Indian Ocean Tsunami

Tourism, the fourth largest contributor of Sri Lanka's foreign exchange was soon brought to halt with the December 2004 Indian Ocean Tsunami. An estimated damage of US$ 250 million to tourist assets and a loss of over 27,000 livelihoods almost ruined the tourist industry of Sri Lanka. An imperative revival process was executed in two phases: immediate relief phase and rapid recovery phase. Immediate relief phase included provision of reassuring measures for tourist victims and notifying the mass media with up to minute tourism situation. The rapid recovery phase was incorporated with a short term recovery process and long term rehabilitation and reconstruction process aimed at recapturing tourist interest, and reestablishing the affected tourist communities and the tourist infrastructure respectively. The lack of a priori disaster management framework and the prevailing security condition of the country impeded the tsunami revival process. This paper documents the impact of the December 2004 Indian Ocean Tsunami on tourism in Sri Lanka and a detailed overview of the recovery strategies adopted in the aftermath of the disaster. Furthermore, it assesses the challenges and way forwards providing guidance to formulate a comprehensive disaster management framework for the tourism sector through the influence of the recovery process.

CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa

BackgroundPatients accessing antiretroviral treatment (ART) programmes in sub-Saharan Africa frequently have very advanced immunodeficiency. Previous data suggest that such patients may have diminished capacity for CD4 cell count recovery.MethodsRates of CD4 cell increase were determined over 48 weeks among ART-naïve individuals (n = 596) commencing ART in a South African community-based ART programme.ResultsThe CD4 cell count increased from a median of 97 cells/μl at baseline to 261 cells/μl at 48 weeks and the proportion of patients with a CD4 cell count <100 cells/μl decreased from 51% at baseline to just 4% at 48 weeks. A rapid first phase of recovery (0–16 weeks, median rate = 25.5 cells/μl/month) was followed by a slower second phase (16–48 weeks, median rate = 7.7 cells/μl/month). Compared to patients with higher baseline counts, multivariate analysis showed that those with baseline CD4 counts <50 cells/μl had similar rates of phase 1 CD4 cell recovery (P = 0.42), greater rates of phase 2 recovery (P = 0.007) and a lower risk of immunological non-response (P = 0.016). Among those that achieved a CD4 cell count >500 cells/μl at 48 weeks, 19% had baseline CD4 cell counts <50 cells/μl. However, the proportion of these patients that attained a CD4 count 200 cells/μl at 48 weeks was lower than those with higher baseline CD4 cell counts.ConclusionPatients in this cohort with baseline CD4 cell counts <50 cells/μl have equivalent or greater capacity for immunological recovery during 48 weeks of ART compared to those with higher baseline CD4 cell counts. However, their CD4 counts remain <200 cells/μl for a longer period, potentially increasing their risk of morbidity and mortality in the first year of ART.

Radiosensitivity of hypoxic and proliferating clonogen in a human lung cancer grown in nude mice

Using cultured and nude mouse tumor cells (IA) derived from a human lung cancer, we studied their radiosensitivity by focusing attention on the dynamics of tumor clonogens. The movement of clonogens in the regrowing IA tumor after irradiation can be divided into three phases: first, the early and rapid survival recovery (PLD repair) phase; second, the delay phase involving a certain lag in survival change; and third, the repopulation phase consisting of two stages: the anoxic repopulation before angiogenesis and the hypoxic repopulation in the presence of a poorly developed vascular network. Clonogens in a regrowing tumor after irradiation were found to actively proliferate even in an anoxic environment before angiogenesis and under the hypoxic conditions prevailing after the formation of a tumor with a poorly developed vascular system. This re-grown tumor was found to be more radioresistant than a sham-treated control tumor. It is believed that these clonogens are genetically selected under hypoxic conditions throughout the process of tumor growth and regrowth, and may be primarily involved in tumor recurrence or accelerated repopulation in fractionated irradiation.

Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation.

Stem cell growth factor (SCGF) is a novel cytokine for primitive hematopoietic progenitor cells. Although it has burst-promoting activity and granulocyte/macrophage colony-promoting activity in vitro, its significance in hematopoiesis in vivo has not been elucidated. In this study, we have established enzyme-linked immunosorbent assay (ELISA) to quantify human SCGF and measured serum cytokines in normal volunteers and 27 patients undergoing stem cell transplantation (SCT), including six autologous and 21 allogeneic transplants. SCGF levels gradually increased after SCT regardless of graft-versus-host disease or type of transplant. The maximum level of SCGF was observed during the rapid granulocyte recovery phase in patients subjected to an autologous transplantation, and during the granulocyte stabilization phase in allogeneic patients. SCGF levels in PBSCT patients began to rise earlier than in BMT patients. Two patients with no increment of SCGF after SCT showed delayed engraftment. The source of SCGF was further analyzed by RT-PCR and we found that SCGF was highly expressed in bone marrow (BM) CD34(+) and CD34(-)CD33(+) cells, but not in BM CD34(-)CD33(-) cells, BM stromal cells and peripheral blood cells. The cell population expressing SCGF in BM possess the colony-forming cell activity. Therefore, serum SCGF can be an indicator of hematopoietic recovery following SCT.

Interaction of Postsynaptic Receptor Saturation with Presynaptic Mechanisms Produces a Reliable Synapse

Synapses that reliably activate their postsynaptic targets typically release neurotransmitter with high probability, are not very sensitive to changes in calcium entry, and depress. We have determined the mechanisms that give rise to these characteristic features at the climbing fiber to Purkinje cell synapse. We find that saturation of presynaptic calcium entry, of presynaptic release, and of postsynaptic receptors combine to produce a postsynaptic response that is near maximal. Postsynaptic receptor saturation also accelerates recovery from depression, in part by accentuating a rapid calcium-dependent recovery phase. Thus, postsynaptic receptor saturation interacts with presynaptic mechanisms to produce highly reliable synapses that can effectively drive their targets even during sustained activation.

Effect of Enhanced UV-B Radiation on Chlorophyll a Fluorescence Parameters in Norway Spruce Needles

Cloned saplings of Norway spruce (7 years old) were continuously exposed to enhanced UV-B irradiation (+ 25 %) over three growing seasons. An analysis of variable chlorophyll a fluorescence was performed at the beginning Gune) and the end (September) of the third growing season in order to evaluate the longterm effects of elevated UV-B irradiation on the primary photosynthetic reactions. A time-dependent response to elevated UV-B radiation was observed. The saturated PPFD electron transport rate (ETR) in the control (C-variant) was 1.92 times that of the exposed plants (E-variant). The midday depression of the maximal photochemical yield of PSII (FV/FM) was deeper in the E-variants, and the extent of this depression, as compared with the C-variants, increased at the end of the growing season. A light-induced decline in the FV/FM ratio was followed by a bi-phasic recovery phase upon return to shade conditions. The rapid recovery phase, possibly related to epoxidation of zeaxanthin, showed a sharper slope in the UV-B exposed E-variants. Thus, the long-term exposure to the elevated UV-B radiation was related to induction of the interconversion between violaxanthin and zeaxanthin. The slow phase of recovery of the Fy/FMratio possibly represents the reactivation of PSII by means of 0 1 protein turnover. The slope of the slow phase of the recovery in E-variants was 0,58 time that of the C-variants at the end of the growing season (i.e. 16 weeks of UV-B illumination). This indicates impairment of the 01 protein turnover as a result of the long-term influence ofUV-B radiation enhancement. The results show that in Norway spruce a long-term exposure to enhanced UV-B radiation under field conditions can be a reason for negative changes at the level of primary photosynthetic reactions.

Force generation upon hydrostatic pressure release in tetanized intact frog muscle fibres.

Single intact muscle fibres isolated from the tibialis anterior muscle of the frog were exposed to hydrostatic pressures of 1-10 MPa, at 2-4 degrees C and sarcomere length of 2.1-2.2 microm. The pressure was rapidly released (ca. 1 ms) to atmospheric level (0.1 MPa) during the plateau of a tetanic contraction (Po) and the resultant tension (= force) transient examined. The pressure release induced tension transient consisted of an initial tension drop coincident with pressure release (ca. 4% Po per MPa, Phase 1), followed by a rapid recovery (Phase 2a) and a slower rise of tension (Phase 2b). Phase 1 was partly due to a length release at fibre ends (ca. 0.1 nm per half-sarcomere per MPa) induced by pressure-release effects on the steel chamber and fibre attachments, and partly due to 'expansion' upon pressure release within muscle fibre (ca. 0.2 nm per half-sarcomere per MPa), probably in the myofilaments and cross-bridges. The rate of tension recovery during phase 2a (ca. 600/s) was comparable to that of the quick tension recovery (T1-T2 transition) reported from moderately fast small length releases; the time course of Phase 2b (rate ca. 40/s) was similar to the late phase of tension rise in a tetanus, and hence compared with Phase 4 (T4) of a length release tension transient. Results are compared with the previously reported findings from analogous experiments on Ca2+ -activated skinned (rabbit) muscle fibres.

Struggling toward easier endoscopy

Struggling toward easier endoscopy

Out-of-equilibrium pH transients in the guinea-pig ventricular myocyte.

1. Following an intracellular alkali load (imposed by acetate prepulsing in CO2/HCO3- buffer), intracellular pH (pHi) of the guinea-pig ventricular myocyte (recorded from intracellular SNARF fluorescence) recovers to control levels. Recovery has two phases. An initial rapid phase (lasting up to 2 min) is followed by a later slow phase (several minutes). Inhibition of sarcolemmal acid-loading carriers (by removal of extracellular Cl-) inhibits the later, slow phase but the initial rapid recovery phase persists. It also persists in the absence of extracellular Na+ and in the presence of the HCO3- transport inhibitor DIDS (4,4-di-isothiocyanatostilbene-2, 2-disulphonic acid). 2. The rapid recovery phase is not evident if the alkali load has been induced by reducing PCO2 (from 10 to 5 %), and it is inhibited in the absence of CO2/HCO3- buffer (i.e. Hepes buffer). It is also slowed by the carbonic anhydrase (CA) inhibitor acetazolamide (ATZ). We conclude that it is caused by buffering of the alkali load through the hydration of intracellular CO2 (CO2-dependent buffering). 3. The time course of rapid recovery is consistent with an intracellular CO2 hydration rate constant (k1) of 0.36 s-1 in the presence of CA activity, and 0.14 s-1 in the absence of CA activity. This latter k1 value matches the literature value for uncatalysed CO2 hydration in free solution. Natural CO2 hydration is accelerated 2.6-fold in the ventricular myocyte by endogenous CA. 4. The rapid recovery phase represents a period when the intracellular CO2/HCO3- buffer is out of equilibrium (OOE). Modelling of the recovery phase using our k1 value, indicates that OOE conditions will normally extend for at least 2 min following a step rise in pHi (at constant PCO2). If CA is inactive, this period can be as long as 5 min. During normal pHi regulation, the recovery rate during these periods cannot be used as a measure of sarcolemmal acid loading since it is a mixture of slow CO2-dependent buffering and transmembrane acid loading. The implication of this finding for quantification of pHi regulation during alkalosis is discussed.

Sarcolemmal mechanisms for pHi recovery from alkalosis in the guinea-pig ventricular myocyte.

1. The mechanism of pHi recovery from an intracellular alkali load (induced by acetate prepulse or by reduction/removal of ambient PCO2) was investigated using intracellular SNARF fluorescence in the guinea-pig ventricular myocyte. 2. In Hepes buffer (pHo 7.40), pHi recovery was inhibited by removal of extracellular Cl-, but not by removal of Na+o or elevation of K+o. Recovery was unaffected by the stilbene drug DIDS (4,4-diisothiocyanatostilbene-disulphonic acid), but was slowed dose dependently by the stilbene drug DBDS (dibenzamidostilbene-disulphonic acid). 3. In 5 % CO2/HCO3- buffer (pHo 7.40), pHi recovery was faster than in Hepes buffer. It consisted of an initial rapid recovery phase followed by a slow phase. Much of the rapid phase has been attributed to CO2-dependent buffering. The slow phase was inhibited completely by Cl-o removal but not by Na+o removal or K+o elevation. 4. At a test pHi of 7.30 in CO2/HCO3- buffer, the slow phase was inhibited 70 % by DIDS. The mean DIDS-inhibitable acid influx was equivalent in magnitude to the HCO3--stimulated acid influx. Similarly, the DIDS-insensitive influx was equivalent to that estimated in Hepes buffer. 5. We conclude that two independent sarcolemmal acid-loading carriers are stimulated by a rise of pHi and account for the slow phase of recovery from an alkali load. The results are consistent with activation of a DIDS-sensitive Cl--HCO3- anion exchanger (AE) to produce HCO3- efflux, and a DIDS-insensitive Cl--OH- exchanger (CHE) to produce OH- efflux. H+-Cl- co-influx as the alternative configuration for CHE is not, however, excluded. 6. The dual acid-loading system (AE plus CHE), previously shown to be activated by a fall of extracellular pH, is thus activated by a rise of intracellular pH. Activity of the dual-loading system is therefore controlled by pH on both sides of the cardiac sarcolemma.

The transient outward current in mice lacking the potassium channel gene Kv1.4.

1. The transient outward current (Ito) plays a prominent role in the repolarization phase of the cardiac action potential. Several K+ channel genes, including Kv1.4, are expressed in the heart, produce rapidly inactivating currents when heterologously expressed, and may be the molecular basis of Ito. 2. We engineered mice homozygous for a targeted disruption of the K+ channel gene Kv1.4 and compared Ito in wild-type (Kv1.4+/+), heterozygous (Kv1.4+/-) and homozygous 'knockout' (Kv1.4-/-) mice. Kv1.4 RNA was truncated in Kv1.4-/- mice and protein expression was absent. 3. Adult myocytes isolated from Kv1.4+/+, Kv1.4+/- and Kv1.4-/- mice had large rapidly inactivating outward currents. The peak current densities at 60 mV (normalized by cellular capacitance, in pA pF-1; means +/- s.e.m.) were 53.8 +/- 5. 3, 45.3 +/- 2.2 and 44.4 +/- 2.8 in cells from Kv1.4+/+, Kv1.4+/- and Kv1.4-/- mice, respectively (P < 0.02 for Kv1.4+/+ vs. Kv1.4-/-). The steady-state values (800 ms after the voltage clamp step) were 30.9 +/- 2.9, 26.9 +/- 3.8 and 23.5 +/- 2.2, respectively (P < 0.02 for Kv1.4+/+ vs. Kv1.4-/-). The inactivating portion of the current was unchanged in the targeted mice. 4. The voltage dependence and time course of inactivation were not changed by targeted disruption of Kv1.4. The mean best-fitting V (membrane potential at 50 % inactivation) values for myocytes from Kv1.4 +/+, Kv1.4+/- and Kv1. 4-/- mice were -53.5 +/- 3.7, -51.1 +/- 2.6 and -54.2 +/- 2.4 mV, respectively. The slope factors (k) were -10.1 +/- 1.4, -8.8 +/- 1.4 and -9.5 +/- 1.2 mV, respectively. The fast time constants for development of inactivation at -30 mV were 27.8 +/- 2.2, 26.2 +/- 5. 1 and 19.6 +/- 2.1 ms in Kv1.4+/+, Kv1.4+/- and Kv1.4-/- myocytes, respectively. At +30 mV, they were 35.5 +/- 2.6, 30.0 +/- 2.1 and 28. 7 +/- 1.6 ms, respectively. The time constants for the rapid phase of recovery from inactivation at -80 mV were 32.5 +/- 8.2, 23.3 +/- 1.8 and 39.0 +/- 3.7 ms, respectively. 5. Nearly the entire inactivating component as well as more than 60 % of the steady-state outward current was eliminated by 1 mM 4-aminopyridine in Kv1.4+/+, Kv1.4+/- and Kv1.4-/- myocytes. 6. Western blot analysis of heart membrane extracts showed no significant upregulation of the Kv4 subfamily of channels in the targeted mice. 7. Thus, Kv1.4 is not the molecular basis of Ito in adult murine ventricular myocytes.

The role of precipitation losses in producing the rapid early recovery phase of the Great Magnetic Storm of February 1986

The possible role of precipitation losses in eroding stormtime ring current is subject to debate. To explore this controversy, the recovery phase of the February 6–10, 1986, great magnetic storm is examined, when intense ion precipitation was observed at midlatitudes by NOAA‐6 and DMSP satellites. This storm period is particularly interesting because the ring current exhibits distinctive two‐phase decay as seen in the Dst index, the early rapid timescale decay corresponding to the intense ion precipitation period described above. Hamilton et al. [1988] concluded, from close agreement between the observed timescale for ring current decay and the theoretical timescale for O+ charge exchange loss, that rapid early recovery phase of this storm resulted from the charge exchange loss of high energy O+; the second and longer decay phase was equated with H+ charge exchange loss. A model of the ring current evolution during this great magnetic storm [Fok et al., 1995] failed to reproduce the observed ring current decay rates, a puzzling result because charge exchange losses were well represented in the ring current model and initial and boundary conditions were taken from the same data set used in the Hamilton et al. [1988] study. A simple energy balance calculation for the global ring current is carried out using (1) either an energy input predicted from upstream solar wind parameters or one calculated from the drift‐loss model output, (2) collisional loss timescales extracted from the drift‐loss model, and (3) precipitation losses estimated from NOAA‐6 and DMSP observations. The energy balance model replicates the evolution of the ring current energy content derived from Active Magnetospheric Particle Tracer Explorers/Charge Composition Explorer (AMPTE/CCE) observations when ion precipitation losses are included and model energy input function is reduced to agree with predictions based upon upstream solar wind parameters. The O+ charge exchange losses and observed global precipitation losses were of equal magnitude in early recovery of the ring current during this great magnetic storm. Later longer decay timescales in the model resulted from a combination of O+ and H+ charge exchange losses; O+ charge exchange losses remained important throughout the model time interval. The present model produces agreement with the AMPTE/CCE estimates of ring current kinetic energy content versus time. Disagreement between the Dst* inferred from the AMPTE/CCE particle measurements and the observed Dst* is an interesting issue needing further explanation.

Impact of temperature acclimation on photosynthesis in the toxic red-tide dinoflagellate Alexandriumfundyense (Ca28)

This study assessed the impact of temperature on the photosynthetic activity in the dino- flagellate Alexandrium fundyense (Ca28) for cultures grown at 75 umol photons rrr2 s~' over a range of temperatures. Increasing light intensity under static temperatures caused a S-fold decrease in the maximum quantum yield for photosystem II (PSII) (FJFm). Carbon fixation rates mirrored high-light depressions in FJFm. Cells in the presence of streptomycin showed an 83% recovery in FJFm; therefore, only a minor proportion of the decline in FJFm was attributable to PSII damage by bright light. For cells transferred to higher temperatures, FJFm was less sensitive to high light, decreasing only 20-40% compared to the 80-90% decrease observed for cells incubated at their ambient growth temperature. For cells shifted to higher temperatures, the rapid recovery phase of FJFm was not present; therefore, cells did not initiate downregulation of PSII. Higher capacity to maintain electron transport, as indicated by the quantum yields, was confirmed by enhanced carbon fixation. Shifts to lower temperatures significantly increased PSII sensitivity to high light. Overall, these relationships reflect the synergy between photosynthetic light and dark reactions which are differentially impacted by changes in temperature.

Mechanotransduction in colonic smooth muscle cells.

We evaluated mechanisms which mediate alterations in intracellular biochemical events in response to transient mechanical stimulation of colonic smooth muscle cells. Cultured myocytes from the circular muscle layer of the rabbit distal colon responded to brief focal mechanical deformation of the plasma membrane with a transient increase in intracellular calcium concentration ([Ca2+]i) with peak of 422.7 +/- 43.8 nm above an average resting [Ca2+]i of 104.8 +/- 10.9 nM (n = 57) followed by both rapid and prolonged recovery phases. The peak [Ca2+]i increase was reduced by 50% in the absence of extracellular Ca2+, while the prolonged [Ca2+]i recovery was either abolished or reduced to less than or = 15% of control values. In contrast, no significant effect of gadolinium chloride (100 microM) or lanthanum chloride (25 microM) on either peak transient or prolonged [Ca2+]i recovery was observed. Pretreatment of cells with thapsigargin (1 microM) resulted in a 25% reduction of the mechanically induced peak [Ca2+]i response, while the phospholipase C inhibitor U-73122 had no effect on the [Ca2+]i transient peak. [Ca2+]i transients were abolished when cells previously treated with thapsigargin were mechanically stimulated in Ca2+-free solution, or when Ca2+ stores were depleted by thapsigargin in Ca2+-free solution. Pretreatment with the microfilament disrupting drug cytochalasin D (10 microM) or microinjection of myocytes with an intracellular saline resulted in complete inhibition of the transient. The effect of cytochalasin D was reversible and did not prevent the [Ca2+]i increases in response to thapsigargin. These results suggest a communication, which may be mediated by direct mechanical link via actin filaments, between the plasma membrane and an internal Ca2+ store.

Simulations of postvagal tachycardia at the single cell pacemaker level: a new hypothesis.

Simulations performed on a single cell model of rabbit sinoatrial node activity after prolonged vagal stimulation have been able to reproduce the known characteristics of cycle length recovery, including the presence of rapid and slow recovery phases and the transient undershoot phenomenon known as postvagal tachycardia (PVT). In the model, the PVT component has been hypothesized to result from the recovery of background levels of the muscarinic K+ current iK,ACh from desensitization due to prolonged exposure to acetylcholine (ACh) neurotransmitter. Other components of the recovery were found to be due to the inactivation of iK,ACh after the hydrolysis of ACh (rapid phase) and the recovery of the hyperpolarizing-activated current i(f) from its ACh-induced inhibition (slow phase). The magnitudes of both the rapid component and the PVT were found to increase linearly with preceding vagally mediated increase in cycle length, whereas the gain of the slow component was found to saturate, reflecting the limited contribution of i(f) inhibition to cycle prolongation.

Membrane properties of mouse anteroventral cochlear nucleus neurons in vitro.

Intracellular recordings were made from neurons of the mouse anteroventral cochlear nucleus (AVCN) in vitro. The whole cochlear nucleus was dissected out and maintained submerged in rapidly flowing artificial CSF. This preparation has the advantages of maintaining cell-to-cell connections and dendritic trees whereas slices and enzymatically separated preparations do not. Recordings were made using current clamp technique in the presence and absence of the ion channel blockers, tetrodotoxin (TTX 1 microM), tetraethylammonium (TEA 20 mM), 4-aminopyridine (4-AP 5 mM) or verapamil (150 microM). Two distinct types of neurons were observed when tested with depolarizing current pulses: one which fired only a single action potential at the onset of stimulation followed by a relative depolarization for the remainder of the stimulus period, and the other which fired a sustained train of action potentials, each followed by a large undershoot, then a rapid recovery phase and the slower depolarization to threshold. The single spike cells (n = 24) had resting membrane potentials of -63.4 +/- 4.7 mV, resistance of 48.4 +/- 29.6 M omega, time constant of 3.47 +/- 3.1 ms, capacitance of 0.081 +/- 0.079 nF. The I/V plot was non-linear above the resting membrane potential and linear below. Spike train cells (n = 24) had resting membrane potentials of -64.2 +/- 4.54 mV, resistance of 69.8 +/- 28.9 M omega, time constant of 6.51 +/- 3.09 ms, capacitance of 0.11 +/- 0.087 nF. The I/V plot was linear both below resting membrane potential and up to threshold for spike firing. TTX abolished spike firing in both cell types. TEA significantly increased the spike duration in both cell types. 4-AP increased the spike duration in spike train cells but not in single spike cells. Verapamil had no effect on the firing properties of both cells but it significantly increased the spike duration of spike train cells. The single spike cells are known to fire rapidly and repetitively in vivo. Injection of sine wave currents caused rapid and repetitive firing suggesting that these cells require hyperpolarization to allow for removal of inactivation. There was a linear relationship between injected depolarizing current and the rate of action potential firing in spike train cells.

Developmental changes of action potential configuration and I(to) in canine epicardium

Developmental changes of the transient outward current (I(to)) and action potential configuration were determined in canine epicardium ranging in age from fetal to 60 wk. The contributions of I(to) to rapid initial repolarization and to terminal repolarization were estimated by measuring the amplitude of phase 1 of the action potential and action potential duration, respectively. Phase 1 amplitude decreased progressively from fetal to 40 wk and remained constant thereafter. Action potential duration decreased from fetal to 2 wk, increased to 20 wk, and tended to decrease thereafter. Peak I(to) at +40 mV increased progressively from 2 to 60 wk. However, I(to) density was less at 2-10 wk than at 20-60 wk. The time constant of decay of I(to) increased with age from 2 to 60 wk, whereas the steady-state voltage dependence of inactivation did not vary with age. The time constant for the initial rapid phase of recovery from inactivation decreased from 2 to 10 wk and remained constant thereafter. The time constant for the more slowly evolving phase did not vary with age. The observation that the age-dependent reduction in phase 1 amplitude did not necessarily coincide with significant increases in I(to) density suggests that maturation of other ionic currents or transport mechanisms may contribute to developmental alterations of phase 1 repolarization.

Reduction of the transient outward potassium current in a canine model of Chagas' disease

The effects of Chagas' disease, an important cause of cardiac arrhythmias and cardiomyopathy, on cellular electrical properties were determined in epicardial tissue from normal dogs and dogs infected with Trypanosoma cruzi for 20-25 days (25 DPI), at the time of maximum parasitemia, and for 125-140 days (140 DPI) after the parasitemia had subsided. At 25 DPI, phase 1 repolarization of the action potential was attenuated and the transient outward current (Ito) was reduced from 10.2 +/- 0.5 to 5.5 +/- 0.6 pA/pF. No differences were apparent between infected and normal cells in the time constants of current decay (25.6 +/- 4.0 and 22.8 +/- 1.3 ms, respectively) or in the steady-state inactivation parameters (V1/2 = -34.1 +/- 3.6 and -34.6 +/- 1.4 mV and k = 6.3 +/- 1.8 and 4.0 +/- 0.3, respectively). The rapid phase of recovery from inactivation was nearly eliminated in infected myocytes, whereas the slower phase was unaffected. Phase 1 repolarization and Ito density at 140 DPI were not significantly different from normal cells. Thus T. cruzi acutely inhibited Ito in epicardial myocytes, an effect that was reversed with abatement of the parasitemia.