ABSTRACT
Objective:To observe the changes of rapidly activated delayed rectifier potassium channel (IKs) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKs and IKs blocker on the incidence ofventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).Methods:Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group.LVH model was prepared.Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH.The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.Results:Compared with cardiac cells in the control group,the interventricular septal thickness at end systole (IVSs),left ventricular posterior wall thickness at end systole (LVPWs),QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (P＜0.05);while IKs densities were significantly reduced [+60 mV:(0.36±0.03) pA/pF vs (0.58±0.05) pA/pF,P＜0.01].However,LVH exerted no significant effect on IKr densities.IKr blocker markedly prolonged the QTc interval (P＜0.01) and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs.In contrast,IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals.IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.Conclusion:The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation of IKs.
ABSTRACT
The growing number of cognitive dysfunction patients is bringing heavy mental and financial burdens to the society and families.Voltage-gated potassium channels (Kv), which consist of delayed rectifier potassium channels and transient outward po -tassium channels , are involved in the incidence of cognitive dysfunction .This review summarized the role of Kv channels in cognitive dysfunction and their relationship with N-methyl-D-aspartic acid receptors ( NMDARs) that play an important role in the process of learning and memory .
ABSTRACT
The effects of protein kinase C (PKC) on the tension and the activity of voltage-dependent delayed rectifier potassium channel (Kv) were examined in normal and passively sensitized human airway smooth muscle (HASM), by measuring tones and whole-cell patch clamp techniques, and the Kv activities and membrane potential (Em) were also detected. The results showed that phorbol 12-myristate 13-acetate (PMA), a PKC activator, caused a concentration-dependent constriction in normal HASM rings. The constriction of the passively sensitized muscle in asthma serum group was significantly higher than that of the normal group (P＜0.05), and the constrictions of both groups were completely abolished by PKC inhibitor Ro31-8220 and calcium channel inhibitor nifedipine. Kv activities of HASM cells were significantly inhibited by PMA, and the Em became more positive, as compared with the DMSO (a PMA menstruum)-treated group (P＜0.01). This effect could be blocked by Ro31-8220 (P＜0.01). It was concluded that activation of PKC could increase the tones of HASM, which might be related to the reduced Kv activity. In passively sensitized HASM rings, this effect was more notable.
ABSTRACT
PURPOSE: Botulium toxin-A (BoTx A) is useful in treating detrusor-sphincter dyssynergia, detrusor hyperreflexia, and refractory overactive bladder. Only the blocking action of acetycholine (ACh) release from nerve endings is the well known aspect of the action mechanism. The aim of this study is to investigate the effects of BoTx A on the detrusor muscle itself. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 3 groups: the control group, the low dose injection group (1unit/ml of BoTx A, 0.5cc), and the high dose injection group (5units/ml of BoTx A, 0.5cc). All rats were either injected with normal saline (control group) or BoTx A (injection groups). Ten days after injection, a strip of the detrusor muscle was harvested. Contraction and relaxation responses of the strips were measured by an isometric force transducer. Contractions were induced by various concentrations of ACh, bethanechol, phenylephrine (PE), high concentrations of potassium (35, 70, 105, 140mM), tetraethylammonium (TEA, 0.1, 1, 10mM), 4-aminopyridine (4-AP, a delayed rectifier K+ antagonist, 0.1, 1, 10mM), and Bay K8644 (a L-type voltage dependent calcium channel opener, 0.1, 1, 10mM). The results were analyzed by ANOVA and the Student's t test. RESULTS: Contractions of the strips were noted when concentrations were above 1mM for TEA and above 0.1mM for 4-AP. A high dose injection as well as a low dose injection of BoTx A had no significant effects on the Ach or bethanechol-induced contractions of the strips compared to the control group. Denervation supersensitivity was not found in the injection groups after the Ach and bethanechol treatments, but the contractility was decreased in high concentrations of potassium (70, 105, 100mM), TEA (10mM), 4-AP (10mM), and Bay K8644 in both the high and low dose injection groups. There was no significant difference in the decrease of contractility between the high and low dose groups with the exception of the Bay K8644 1M treatment. CONCLUSIONS: BoTx seems to have some direct effects on decreasing the contractility of the detrusor muscle by increasing the delayed rectifier K+ channel activity and decreasing the L-type voltage dependent calcium channel activity.
Subject(s)
Animals , Rats , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester , 4-Aminopyridine , Ataxia , Bethanechol , Botulinum Toxins, Type A , Calcium Channels , Calcium , Denervation , Nerve Endings , Phenylephrine , Potassium , Rats, Sprague-Dawley , Reflex, Abnormal , Relaxation , Tea , Tetraethylammonium , Transducers , Urinary Bladder , Urinary Bladder, OveractiveABSTRACT
Aim To explore the effect of the morphine(MP) on the Kv channel in bronchial smooth muscle in guinea-pigs (GPBSM) and expressions of the Kv 1.5 mRNA and protein . Methods The effect of the MP on the Kv channel was studied by patch clamp recording in GPBSM and expressions of the Kv 1.5 mRNA and protein were measured by Western-blot and RT-PCR techniques. Results Morphine remarkably restrained the Kv channel current and the expression of the Kv 1.5 mRNA and protein in cultured GPBSM (n=6, each group, P
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AIM To clarify the mechanism of berberine on mobility diarrhea by investigating the effects of berberine on calcium-activated potassium current I K(Ca) and delayed-rectifier potassium channel current I K(V) of guinea pig colonic smooth muscle cells. METHODS Single guinea pig colonic smooth muscle cells was isolated by collagenase; The effects of berberine on I K(Ca) and I K(V) were detected by using patch clamp technique, under the conventional whole cell patch clamp mode. RESULTS 10, 50, 100 ?mol?L -1 berberine inhibited I K(Ca) of guinea pig colonic smooth muscle cells significantly (P