Characterisation of development and electrophysiological mechanisms underlying rhythmicity of the avian lymph heart

Despite significant advances in tissue engineering such as the use of scaffolds, bioreactors and pluripotent stem cells, effective cardiac tissue engineering for therapeutic purposes has remained a largely intractable challenge. For this area to capitalise on such advances, a novel approach may be to unravel the physiological mechanisms underlying the development of tissues that exhibit rhythmic contraction yet do not originate from the cardiac lineage. Considerable attention has been focused on the physiology of the avian lymph heart, a discrete organ with skeletal muscle origins yet which displays pacemaker properties normally only found in the heart. A functional lymph heart is essential for avian survival and growth in ovo. The histological nature of the lymph heart is similar to skeletal muscle although molecular and bioelectrical characterisation during development to assess mechanisms that contribute towards lymph heart contractile rhythmicity have not been undertaken. A better understanding of these processes may provide exploitable insights for therapeutic rhythmically contractile tissue engineering approaches in this area of significant unmet clinical need. Here, using molecular and electrophysiological approaches, we describe the molecular development of the lymph heart to understand how this skeletal muscle becomes fully functional during discrete in ovo stages of development. Our results show that the lymph heart does not follow the normal transitional programme of myogenesis as documented in most skeletal muscle, but instead develops through a concurrent programme of precursor expansion, commitment to myogenesis and functional differentiation which offers a mechanistic explanation for its rapid development. Extracellular electrophysiological field potential recordings revealed that the peak-to-peak amplitude of electrically evoked local field potentials elicited from isolated lymph heart were significantly reduced by treatment with carbachol; an effect that could be fully reversed by atropine. Moreover, nifedipine and cyclopiazonic acid both significantly reduced peak-to-peak local field potential amplitude. Optical recordings of lymph heart showed that the organ’s rhythmicity can be blocked by the HCN channel blocker, ZD7288; an effect also associated with a significant reduction in peak-to-peak local field potential amplitude. Additionally, we also show that isoforms of HCN channels are expressed in avian lymph heart. These results demonstrate that cholinergic signalling and L-type Ca2+ channels are important in excitation and contraction coupling, while HCN channels contribute to maintenance of lymph heart rhythmicity

Three-Point Boundary Value Problems for Conformable Fractional Differential Equations

We study a fractional differential equation using a recent novel concept of fractional derivative with initial and three-point boundary conditions. We first obtain Green's function for the linear problem and then we study the nonlinear differential equation

Bistable behaviour in squeezed vacua: II. Stability analysis and chaos

Linear stability analysis and (numerical) investigation of the periodic and chaotic self-pulsing behaviour are presented for the Maxwell-Bloch equations of a bistable model in contact with a squeezed vacuum field. Effect of the squeeze phase parameter on the period doubling bifurcation that preceeds chaos is examined for the adiabatic and non-adiabatic regimes

Bistable behaviour in squeezed vacua: I. Stationary analysis

A time-independent theoretical and numerical analysis of an optical bistable model of two-level atoms in a ring cavity, driven by a coherent field and in contact with a squeezed vacuum field is presented in the two cases of absorptive and dispersive optical bistability (OB). In the former case, a suitable choice of the phase of the squeezed vacuum field reduces the threshold for OB to occur compared with the normal vacuum case. In the latter case, regions of OB are identified as one or two disconnected simple closed curves depending on the cooperation parameter 0pt[0pt]$C \stackrel{> }{< } C_{\rm crit}^{\max}$: $C_{\rm crit}^{\max}$ is the maximum possible value of the critical value of C at fixed values of the squeezed vacuum field parameters. Phase switching effects between different (output) states of the system is investigated in detail. In the absorptive case, one- or two-way optical switching is possible depending on 0pt[0pt]$C \stackrel{> }{< } C_{\rm crit}^{\max}$. We also present results which demonstrate more complicated switching behaviour in the dispersive case