Biomedical subjects

Haruo Honjo

Publications and source records attributed to Haruo Honjo.

25 records · Page 2Linked to original sources

PubMed2003

Asymptotic function for multigrowth surfaces using power-law noise.

Numerical simulations are used to investigate the multiaffine exponent alpha(q) and multigrowth exponent beta(q) of ballistic deposition growth for noise obeying a power-law distribution. The simulated values of beta(q) are compared with the asymptotic function beta(q)=1/q that is approximated from the power-law behavior of the distribution of height differences over time. They are in good agreement for large q. The simulated alpha(q) is found in the range 1/q< or =alpha(q)< or =2/(q+1). This implies that large rare events tend to break the Kardar-Parisi-Zhang universality scaling law at higher order q.

Journal Article↗

PubMed2003

Sophisticated architecture is required for the sinoatrial node to perform its normal pacemaker function.

The heart's pacemaker, the sinoatrial node, does not consist of a group of uniform sinoatrial node cells embedded in atrial muscle. Instead, it is a heterogeneous tissue with multiple cell types and a complex structure. Evidence suggests that from the periphery to the center of the sinoatrial node, there is a gradient in action potential shape, pacemaking, ionic current densities, connexin expression, Ca2+ handling, myofilament density, and cell size. This complexity may be necessary for the sinoatrial node to pacemake under diverse conditions, drive the more hyperpolarized atrial muscle, and resist proarrhythmic perturbations.

Action Potentials↗

PubMed2002

Ionic mechanisms of acquired QT prolongation and torsades de pointes in rabbits with chronic complete atrioventricular block.

BACKGROUND: The ionic basis of acquired QT prolongation and torsade de pointes (TdP) unrelated to drugs is not fully understood. METHODS AND RESULTS: We created a rabbit model with chronic complete atrioventricular block (AVB) (n=34), which showed prominent QT prolongation (by 120%), high incidence of spontaneous TdP (71%), and cardiac hypertrophy. Patch-clamp experiments were performed in left ventricular myocytes from 9 rabbits (8 with TdP, 1 without TdP) at approximately 21 days of AVB and from 8 sham-operated controls with sinus rhythm. Action potential duration was prolonged in AVB myocytes compared with control (+61% at 0.5 Hz, +21% at 3 Hz). Both rapidly and slowly activating components of the delayed rectifier K(+) current (I(Kr) and I(Ks)) in AVB myocytes were significantly smaller than in control by 50% and 55%, respectively. There was no significant difference in Ca(2+)-independent transient outward current (I(to1)). L-type Ca(2+) current (I(Ca,L)) in control and AVB myocytes was similar in peak amplitude, but the half voltage for activation was shifted to the negative direction (5.9 mV) in AVB myocytes. Voltage dependence of I(Ca,L) inactivation was not different in control and AVB myocytes. The inward rectifier K(+) current (I(K1)) significantly increased in AVB myocytes compared with control. CONCLUSIONS: In the rabbit, chronic AVB leads to prominent QT prolongation and high incidence of spontaneous TdP. Downregulation of both I(Kr) and I(Ks) in association with altered I(Ca,L) activation kinetics may underlie the arrhythmogenic ventricular remodeling.

Action Potentials↗

PubMed2002

Heterogeneous expression of connexins in rabbit sinoatrial node cells: correlation between connexin isotype and cell size.

OBJECTIVE: Intercellular coupling through gap junctions allows the morphologically and functionally heterogeneous sinoatrial node to synchronize and drive the atrial muscle. The purpose of this study was to identify the connexin isotypes expressed by sinoatrial node cells and to analyse the density of connexins in relation to cell size. METHODS: Labeling for the different connexins using isotype-specific antibodies was assessed in cells isolated from the rabbit sinoatrial node by immunoconfocal microscopy. RESULTS: Sinoatrial node cells with a cell projection area smaller than 800 microm(2) were devoid of immunolabeling for connexin43. Such small cells showed high levels of connexin45 labeling (compared to that in large cells) and low levels of connexin40 labeling. Sinoatrial node cells with a projection area between 800 and 1200 microm(2) had a lower amount of connexin45 label and again a small amount of connexin40 but an increased amount of connexin43 label. In the larger sinoatrial node cells, some colocalization of connexin45 and connexin43 immunolabeled spots was observed. CONCLUSIONS: Rabbit sinoatrial node cells are heterogeneous in terms of connexin expression, and there is a clear cell size-dependence in pattern of connexin expression. Small (putative central) cells express connexin45 but not connexin43, whereas larger (putative peripheral) cells express both connexin45 and connexin43. The co-localization of connexin43 and connexin45 in larger cells raises the possibility that heterotypic or heteromeric connexin43/connexin45 channels could be present in gap junctions at the periphery of the sinoatrial node.

Animals↗

PubMed2002

Are we lost in the labyrinth of the sinoatrial node pacemaker mechanism?

Despite extensive electrophysiologic studies performed to date, the ionic mechanisms of sinoatrial node pacemaker activity are unclear. This article highlights three recent topics associated with this issue: (1) sustained inward current (Ist)); (2) the role of Ca2+ release from the sarcoplasmic reticulum; and (3) the role of L-type Ca2+ current (I(Ca,L)). New observations on these topics seem to make the scenario of the pacemaker mechanism increasingly complex. However, such complexity and diversity of ionic events and their orchestration may be important for the sinoatrial node to perform its robust pacemaking activity under a variety of pathophysiologic circumstances.

Animals↗

PubMed2002

A dynamic action potential model analysis of shock-induced aftereffects in ventricular muscle by reversible breakdown of cell membrane.

To elucidate the subcellular mechanism underlying the aftereffects of high-intensity dc shocks, a small pore, which mimics reversible breakdown of the cell membrane (electroporation), was incorporated into the phase-2 Luo-Rudy (L-R) model of ventricular action potentials. The pore size was set to occupy 0.15%-4.25% of the total cell membrane during the 10-ms shock. The pore was assumed to decrease after the shock exponentially with a time constant of 100-1,400 ms to simulate resealing process. In normal myocytes, the pore formation results in a delay of repolarization of the shocked action potential, which is followed by prolonged depolarization and oscillation of membrane potential like early afterdepolarization (EAD). Time- and voltage-dependent changes in the delayed rectifier K+ currents (IKr, IKs) in combination with those of L-type Ca2+ current (ICa,(L)) and ion flux through the pore (I(pore)) are responsible for the potential changes. Spontaneous excitation from the oscillation depends on activation of ICa,(L). In myocytes overloaded with Na+ and Ca2+ secondary to 90% inhibition of Na+-K+ pump, the pore formation results in a delay of repolarization of the shocked action potential, which is followed by slower cyclic depolarization in response to spontaneous release of Ca2+ from the sarcoplasmic reticulum (SR). This delayed afterdepolarization-type oscillation is abolished by complete block of Ca2+ release from the SR. These findings suggest that high-intensity electric field application will cause arrhythmogenic responses through a transient rupture of sarcolemma with different subcellular events in ventricular cells under normal and pathological conditions.

Action Potentials↗

PubMed2002

Regulation of capacitative and noncapacitative receptor-operated Ca2+ entry by rho-kinase in tracheal smooth muscle.

To determine the mechanisms of Ca2+ mobilization induced by receptor agonists, we examined the role of Rho-kinase on the sarcoplasmic reticulum (SR) Ca2+ stores-dependent and -independent Ca2+ influx in guinea pig tracheal smooth muscle (TSM). Isometric tension and intracellular Ca2+ concentration ([Ca2+]i) were simultaneously measured using fura-2-loaded tissues. Depletion of the SR Ca2+ stores by thapsigargin caused an increase in [Ca2+]i and contraction, demonstrating capacitative Ca2+ entry (CCE). Because CCE was not inhibited by nifedipine, voltage-operated Ca2+ channels are not involved in CCE. Under the condition that CCE is fully activated, methacholine (MCh) and histamine caused further increases in [Ca2+]i and tension, demonstrating noncapacitative receptor-operated Ca2+ entry (non-CCE). The Ca2+ influx and contraction via non-CCE was inhibited by Y-27632, a Rho-kinase inhibitor, in a concentration-dependent fashion. In contrast, Y-27632 did not affect thapsigargin-induced CCE. Cytochalasin D, which disrupts actin cytoskeleton, inhibited contraction induced by CCE or MCh with no change in [Ca2+]i. Our results indicate that not only CCE but also non-CCE exist in TSM and that the latter is regulated by Rho-kinase, independent of actin cytoskeleton. In conclusion, Ca2+ influx regulated by the RhoA/Rho-kinase pathway may play a functional role in contraction by agonists.

Actins↗