Contemporary educational methods in periodontology.

AIM The 1st European Workshop on Periodontal Education in 2009 made recommendations regarding the scope of periodontal education at undergraduate (UG), postgraduate (PG) and continuing professional development (CPD) levels, defining competencies and learning outcomes that were instrumental at the time in helping to define periodontal teaching curricula. The 19th European Workshop on Periodontology and 2nd European Consensus Workshop on Education in Periodontology (Education in Periodontology in Europe) was held in 2023 to identify changes and future developments in periodontal education (including those informed by the COVID-19 pandemic) and embracing methods and formats of periodontal teaching and training. The aim of this review was to assess current knowledge regarding education methods in periodontology, including traditional face-to-face (F2F) teaching and the move to student-centred methods, virtual learning methods and use of digital technology, as well as blended teaching and learning (including teaching delivery and assessment) at UG, PG and CPD levels. MATERIALS AND METHODS Systematic searches were conducted to identify relevant studies from the literature. Data were extracted and descriptive summaries collated. RESULTS The pandemic was a major disruptor of traditional F2F teaching but provided opportunities for rapid implementation of alternative and supplementary teaching methods. Although online learning has become an integral part of periodontal education, teachers and learners alike favour some form of F2F teaching. Blended teaching and learning are feasible in many areas of periodontal education, both for knowledge and skills acquisition as well as in assessment. Student-centred methods and blended approaches such as the flipped classroom seem highly effective, and online/virtual classrooms with both synchronous and asynchronous lectures are highly valued. Learning with haptic methods and virtual reality (VR) enhances the educational experience, especially when VR is integrated with traditional methods. The quality of the teacher continues to be decisive for the best knowledge transfer in all its forms. CONCLUSIONS Live F2F teaching continues to be highly trusted; however, all types of student-centred and interactive forms of knowledge transfer are embraced as enhancements. While digital methods offer innovation in education, blended approaches integrating both virtual and traditional methods appear optimal to maximize the achievement of learning outcomes. All areas of periodontal education (UG, PG and CPD) can benefit from such approaches; however, more research is needed to evaluate their benefits, both for knowledge transfer and skills development, as well as in assessment

Effects of muscarinic receptor stimulation on Ca2+ transient, cAMP production and pacemaker frequency of rabbit sinoatrial node cells

We investigated the contribution of the intracellular calcium (Cai2+) transient to acetylcholine (ACh)-mediated reduction of pacemaker frequency and cAMP content in rabbit sinoatrial nodal (SAN) cells. Action potentials (whole cell perforated patch clamp) and Cai2+ transients (Indo-1 fluorescence) were recorded from single isolated rabbit SAN cells, whereas intracellular cAMP content was measured in SAN cell suspensions using a cAMP assay (LANCE®). Our data show that the Cai2+ transient, like the hyperpolarization-activated “funny current” (If) and the ACh-sensitive potassium current (IK,ACh), is an important determinant of ACh-mediated pacemaker slowing. When If and IK,ACh were both inhibited, by cesium (2 mM) and tertiapin (100 nM), respectively, 1 μM ACh was still able to reduce pacemaker frequency by 72%. In these If and IK,ACh-inhibited SAN cells, good correlations were found between the ACh-mediated change in interbeat interval and the ACh-mediated change in Cai2+ transient decay (r2 = 0.98) and slow diastolic Cai2+ rise (r2 = 0.73). Inhibition of the Cai2+ transient by ryanodine (3 μM) or BAPTA-AM (5 μM) facilitated ACh-mediated pacemaker slowing. Furthermore, ACh depressed the Cai2+ transient and reduced the sarcoplasmic reticulum (SR) Ca2+ content, all in a concentration-dependent fashion. At 1 μM ACh, the spontaneous activity and Cai2+ transient were abolished, but completely recovered when cAMP production was stimulated by forskolin (10 μM) and IK,ACh was inhibited by tertiapin (100 nM). Also, inhibition of the Cai2+ transient by ryanodine (3 μM) or BAPTA-AM (25 μM) exaggerated the ACh-mediated inhibition of cAMP content, indicating that Cai2+ affects cAMP production in SAN cells. In conclusion, muscarinic receptor stimulation inhibits the Cai2+ transient via a cAMP-dependent signaling pathway. Inhibition of the Cai2+ transient contributes to pacemaker slowing and inhibits Cai2+-stimulated cAMP production. Thus, we provide functional evidence for the contribution of the Cai2+ transient to ACh-induced inhibition of pacemaker activity and cAMP content in rabbit SAN cells

Atrio-sinus interaction demonstrated by blockade of the rapid delayed rectifier current

BACKGROUND: Proper pacemaking of the heart requires a specific organization of the sinoatrial (SA) node. The SA node drives the surrounding atrium but needs to be protected from its hyperpolarizing influence, which tends to suppress pacemaker activity. It has been suggested that the hyperpolarizing atrial influence is minimal at the site of the central nodal area. METHODS AND RESULTS: Atrio-sinus interaction was assessed by specific depolarization of the SA node by blocking the HERG-encoded rapid delayed rectifier current (I(K,r)) with the drug E-4031. In the SA node, E-4031 (1 micromol/L) changed action potential configuration drastically but never resulted in pacemaker arrest. In the atrium, E-4031 did not affect the membrane resting potential, thereby leaving the normal hyperpolarizing load on the SA node intact. When the SA node was sectioned into strips and subsequently separated from the atrium, spontaneous electrical activity of the strip containing the primary pacemaker ceased on I(K,r) blockade. When not separated from the atrium, I(K,r) blockade never resulted in pacemaker arrest. A similar effective atrio-sinus interaction was demonstrated in computer simulations. CONCLUSIONS: Our results demonstrate that the atrium provides an effective hyperpolarizing load on the central SA nodal area and is at least one of the controlling mechanisms for normal pacemaking function. The present study can be of help in understanding why patients with long-QT2 syndrome secondary to a mutation in HERG do not show sinus arres

Ionic remodeling of sinoatrial node cells by heart failure

Background-In animal models of heart failure (HF), heart rate decreases as the result of an increase in intrinsic cycle length of the sinoatrial node (SAN). In this study, we evaluate the HF-induced remodeling of membrane potentials and currents in SAN cells. Methods and Results-SAN cells were isolated from control rabbits and rabbits with volume and pressure overload induced HF and patch-clamped to measure their electrophysiological properties. HF cells were not hypertrophied (capacitance, mean +/- SEM, 52 +/- 3 versus 50 +/- 4 pF in control). HF increased intrinsic cycle length by 15% and decreased diastolic depolarization rate by 30%, whereas other action potential parameters were unaltered. In HF, the hyperpolarization-activated "pacemaker" current (I-f) and slow component of the delayed rectifier current (I-Ks) were reduced by 40% and 20%, respectively, without changes in voltage dependence or kinetics. T-type and L-type calcium current, rapid and ultrarapid delayed rectifier current, transient outward currents, and sodium-calcium exchange current were unaltered. Conclusions-In single SAN cells of rabbits with HF, intrinsic cycle length is increased as the result of a decreased diastolic depolarization rate rather than a change in action potential duration. HF reduced both I-f and I-Ks density. Since I-Ks plays a limited role in pacemaker activity, the HF-induced decrease in heart rate is attributable to remodeling of I-

Ca(2+)-activated Cl(-) current in rabbit sinoatrial node cells

The Ca(2+)-activated Cl(-) current (I(Cl(Ca))) has been identified in atrial, Purkinje and ventricular cells, where it plays a substantial role in phase-1 repolarization and delayed after-depolarizations. In sinoatrial (SA) node cells, however, the presence and functional role of I(Cl(Ca)) is unknown. In the present study we address this issue using perforated patch-clamp methodology and computer simulations. Single SA node cells were enzymatically isolated from rabbit hearts. I(Cl(Ca)) was measured, using the perforated patch-clamp technique, as the current sensitive to the anion blocker 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS). Voltage clamp experiments demonstrate the presence of I(Cl(Ca)) in one third of the spontaneously active SA node cells. The current was transient outward with a bell-shaped current-voltage relationship. Adrenoceptor stimulation with 1 microM noradrenaline doubled the I(Cl(Ca)) density. Action potential clamp measurements demonstrate that I(Cl(Ca)) is activate late during the action potential upstroke. Current clamp experiments show, both in the absence and presence of 1 microM noradrenaline, that blockade of I(Cl(Ca)) increases the action potential overshoot and duration, measured at 20 % repolarization. However, intrinsic interbeat interval, upstroke velocity, diastolic depolarization rate and the action potential duration measured at 50 and 90 % repolarization were not affected. Our experimental data are supported by computer simulations, which additionally demonstrate that I(Cl(Ca)) has a limited role in pacemaker synchronization or action potential conduction. In conclusion, I(Cl(Ca)) is present in one third of SA node cells and is activated during the pacemaker cycle. However, I(Cl(Ca)) does not modulate intrinsic interbeat interval, pacemaker synchronization or action potential conductio

Role of protein kinase C in anterior pituitary hormone release

The effects of intercellular coupling conductance on the activity of two electrically coupled isolated rabbit sinoatrial nodal cells were investigated. A computer-controlled version of the “coupling clamp” technique was used in which isolated sinoatrial nodal cells, not physically in contact with each other, were electrically coupled at various values of ohmic coupling conductance, mimicking the effects of mutual interaction by electrical coupling through gap junctional channels. We demonstrate the existence of four types of electrical behavior of coupled spontaneously active cells. As the coupling conductance is progressively increased, the cells exhibit: (a) independent pacemaking at low coupling conductances, (b) complex dynamics of activity with mutual interactions, (c) entrainment of action potential frequency at a 1:1 ratio with different action potential waveforms, and (d) entrainment of action potentials at the same frequency of activation and virtually identical action potential waveforms. The critical value of coupling conductance required for 1:1 frequency entrainment was <0.5 nS in each of the five cell pairs studied. The common interbeat interval at a relatively high coupling conductance (10 nS), which is sufficient to produce entrainment of frequency and also identical action potential waveforms, is determined most by the intrinsically faster pacemaker cell and it can be predicted from the diastolic depolarization times of both cells. Evidence is provided that, at low coupling conductances, mutual pacemaker synchronization results mainly from the phase-resetting effects of the action potential of one cell on the depolarization phase of the other. At high coupling conductances, the tonic, diastolic interactions become more important

Atrial fibrillation in KCNE1-null mice

Although atrial fibrillation is the most common serious cardiac arrhythmia, the fundamental molecular pathways remain undefined. Mutations in KCNQ1, one component of a sympathetically activated cardiac potassium channel complex, cause familial atrial fibrillation, although the mechanisms in vivo are unknown. We show here that mice with deletion of the KCNQ1 protein partner KCNE1 have spontaneous episodes of atrial fibrillation despite normal atrial size and structure. Isoproterenol abolishes these abnormalities, but vagomimetic interventions have no effect. Whereas loss of KCNE1 function prolongs ventricular action potentials in humans, KCNE1-/- mice displayed unexpectedly shortened atrial action potentials, and multiple potential mechanisms were identified: (1) K+ currents (total and those sensitive to the KCNQ1 blocker chromanol 293B) were significantly increased in atrial cells from KCNE1-/- mice compared with controls, and (2) when CHO cells expressing KCNQ1 and KCNE1 were pulsed very rapidly (at rates comparable to the normal mouse heart and to human atrial fibrillation), the sigmoidicity of IKs activation prevented current accumulation, whereas cells expressing KCNQ1 alone displayed marked current accumulation at these very rapid rates. Thus, KCNE1 deletion in mice unexpectedly leads to increased outward current in atrial myocytes, shortens atrial action potentials, and enhances susceptibility to atrial fibrillatio

Conduction slowing by the gap junctional uncoupler carbenoxolone

Background: Cellular electrical coupling is essential for normal propagation of the cardiac action potential, whereas reduced electrical coupling is associated with arrhythrmas. Known cellular uncoupling agents have severe side effects on membrane ionic currents. We investigated the effect of carbenoxolone on cellular electrical coupling, membrane ionic currents, and atrial and ventricular conduction. Methods and Results: In isolated rabbit left ventricular and right atrial myocytes, carbenoxolone (50 mumol/l) had no effect on action potential characteristics. Calcium, potassium, and sodium currents remained unchanged. Dual current clamp experiments on poorly coupled cell pairs revealed a 21 +/- 3% decrease in coupling conductance by carbenoxolone (mean +/- S.E.M., n = 4, p <0.05). High-density activation mapping was performed in intact rabbit atrium and ventricle during Langendorff perfusion of the heart. The amplitude of the Laplacian of the electrograms, a measure of coupling current in intact hearts, decreased from 1.45 +/- 0.66 to 0.75 +/- 0.51 muA/mm(3) (mean +/- SD, n = 32, p <0.05) after 15 min of carbenoxolone. Carbenoxolone reversibly decreased longitudinal and transversal conduction velocity from 66 +/- 15 to 49 +/- 16 cm/s and from 50 +/- 14 to 35 +/- 15 cm/s in ventricle, respectively (mean SD, n = 5, both p <0.05). In atrium, longitudinal and transversal conduction, velocity decreased from 80 +/- 29 to 60 +/-16 cm/s and from 49 +/- 10 to 38 +/- 10 cm/s (mean SD, n = 8, both p <0.05). Conclusions: Carbenoxolone-induced uncoupling causes atrial and ventricular conduction slowing without affecting cardiac membrane currents. Activation delay is larger in poorly coupled cells. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserve

Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria

The sinoatrial node initiates the heartbeat and controls the rate and rhythm of contraction, thus serving as the pacemaker of the heart. Despite the crucial role of the sinoatrial node in heart function, the mechanisms that underlie its specification and formation are not known. Tbx3, a transcriptional repressor required for development of vertebrates, is expressed in the developing conduction system. Here we show that Tbx3 expression delineates the sinoatrial node region, which runs a gene expression program that is distinct from that of the bordering atrial cells. We found lineage segregation of Tbx3-negative atrial and Tbx3-positive sinoatrial node precursor cells as soon as cardiac cells turn on the atrial gene expression program. Tbx3 deficiency resulted in expansion of expression of the atrial gene program into the sinoatrial node domain, and partial loss of sinoatrial node-specific gene expression. Ectopic expression of Tbx3 in mice revealed that Tbx3 represses the atrial phenotype and imposes the pacemaker phenotype on the atria. The mice displayed arrhythmias and developed functional ectopic pacemakers. These data identify a Tbx3-dependent pathway for the specification and formation of the sinoatrial node, and show that Tbx3 regulates the pacemaker gene expression program and phenotype