Permissive action of thyroid hormone at the level of Ca channel and responsible mechanisms underlying thyroid hormone-induced change in myocardial contractile state and $T_3-induced$ arrhythmias were investigated in rabbit ventricular or atrial myocytes using whole cell patch clamp technique. Single cells were isolated by Langendorff perfusion with collagenase. Cardiac myocytes were incubated in $low-Cl^-,$, $high-K^+$ medium containing $1_{\mu}M\;L-triiodothyronine\;(T_3)$ at $4^{\circ}C$ for 2.10 hours. The calcium currrent $(I_{Ca})$ was increased in $T_3$ loaded cells, however, the shape of current voltage curve and reverse potential did not altered. Cyclic AMP, cyclic GMP, isoprenaline and 3-isobutyl-1-methyl-xanthine increased $I_{Ca}$ in euthyroid and hyperthyroid conditions, and acetylcholine blocked the increase of $I_{Ca}\;in\;T_3$ loaded cells. The amplitude of $I_{Ca}$ was much larger after perfusing cGMP than cGMP in both conditions, whereas the degree of increase of $I_{Ca}$ was greater after perfusing cAMP than cGMP in $T_3$ loaded cells. The degree of increase of $I_{Ca}$ after perfusing isoprenaline or IBMX also was greater in $T_3$ loaded cells than in control cells. Background current induced by isoprenaline also increased in $T_3$ loaded cells. The Ca release dependent inward current was increased in amplitude but its activation and inactivation time course was not changed in $T_3$ loaded cells. Activation of Na pump current was not changed in $T_3$ loaded cells. From the above results it is suggested that thyroid hormone induced increase in the contractile state of cardiac myocytes are accompanied by augmented $I_{Ca}$ and the increase of Ca release from sarcoplasmic reticulum and the permissive action of thyroid hormone to catecholamines could induce arrhythmias through the increase of $I_{Ca}$ and background current.

It is well known that chromaffin cells of adrenal medulla secrete catecholamine in response to sympathetic nerve activation and the influx of $Ca^{2+}$ through the voltage dependent $Ca^{2+}$ channels (VDCC) in the cell membrane do a major role in this secretory process. In this study, we explored the effect of divalent cations on VDCC of rat chromaffin cells. Rat (Sprague-Dawley rat, 150-250 gm) chromaffin cells were isolated and cultured. Standard giga seal, whole cell recording techniques were employed to study $Ca^{2+}$ current with external and internal solutions that could effectively isolate VDCC currents $(NMG\;in\;external\;and\;TEA\;and\;Cs^{2+}\;in\;internal\;solution)$. The voltage dependence and the inactivation time course of VDCC in our cells were identical to those of bovine chromaffin cells. A persistent inward current was first activated by depolarizing step pulse from the holding potential (H.P.) of -80 mV to -40 mV, increased to maximum amplitude at around +10 mV, and became smaller with progressively higher depolarizing pulses to reverse at around +60 mV. The inactivation time constant $(\tau)$, fitted from the long duration test potential (2 sec) was $1295.2{\pm}126.8$ msec $(n=20,\;1\;day\;of\;culture,\;mean\;{\pm}S.E.M.)$ and the kinetic parameters were not altered along the culture duration. Nicardipine $(10\;{\mu}M)$ blocked the current almost completely. Among treated divalent cations such as $Cd^{2+},\;Co^{2+},\;Ni^{2+},\;Zn^{2+}\;and\;,Mn^{2+},\;Cd^{2+}$ was the most potent blocker on VDCC. When the depolarizing step pulse from -80 mV to 10 mV was applied, the equilibrium dissociation constant $(K_d)$ of $Cd^{2+}\;was\;39\;{\mu}M,\;K_d\;of\;Co^{2+}\;was\;100\;{\mu}M\;and\;K_d\;of\;Ni^{2+}];was];780{\mu}M.$ The principal findings of this study are as follows. First, the majority of $Ca^{2+}$ channels in rat chromaffin cells are well classified to L-type $Ca^{2+}$ channel in the view of kinetics and pharmacology. Second, all divalent cations tested could block the $Ca^{2+}$ current and the most potent blocker among the tested was $Cd^{2+}$.

The present study was undertaken to examine if endogenous nitric oxide is partly responsible for the high calcium induced vasorelaxation in vitro. Isolated porcine coronary arterial rings were suspended in the tissue chamber and their changes in isometric tension were recorded. KCI little affected the vascular tension in the calcium free media, but subsequent addition of cumulative doses of $CaCl_3$ from 1 to 40 mM caused a contraction followed by complete relaxation. The maximum tension was noted at the calcium concentration in the media of 5 mM, and then the tension progressively declined at 10-40 mM. The relaxation was slightly attenuated in the endothelium-denuded preparation. The relaxation was converted into a contraction by the addition of methylene blue. The relaxation response was not affected in the presence of indomethacin, but was significantly attenuated by $N^w-nitro-L-arginine$ methyl ester pretreatment. These results suggest that the calcium induced vasorelaxation is in part attributable to the release of endogenous nitric oxide.

The effects of $Cd^{2+}$ on spontaneous contraction, and the contractures induced by $0mM\;Na^+,\;60mM\;K^+\;and\;10^{-6}\;M$ acetylcholine, 1mM caffeine were studied in order to elucidate diverse actions of $Cd^{2+}$ on the $Ca^{2+}$ mobilization related with contractility in the antral circular muscle of guinea pig stomach. $Cd^{2+}$ inhibited the spontaneous contraction in a does dependent manner $(10^{-6}\;M\;10^{-4}\;M).\;Cd^{2+}\;(3{\times}10^{-5}M)$ suppressed 60 mM $K^+$ induced contracture composed or a phasic and a tonic response and the increased tonic response by the increased external $Ca^{2+}$ concentration. $Cd^{2+}$ also suppressed acetylcholine induced contracture composed of repetitive phasic and a tonic component and the increased tonic response by the increased external $Ca^{2+}$ concentration. Caffeine in the concentration of 1mM evoked contracture but $Cd^{2+}$ suppressed the contracture. $Cd^{2+}$ suppressed the amplitude of the $Na^+$ tee contracture dose dependently and the amplitude of $Na^+$ free contracture almost decreased to 20% of control amplitude in the concentration of $10^{-4}\;M\;Cd^{2+}$. From the above results, it is suggested that $Cd^{2+}$ may inhibit not only $Ca^{2+}$ influx via voltage sensitive, receptor operated $Ca^{2+}$ channel and Na/ca exchange but also intracellular $Ca^{2+}$ release from the sarcoplasmic reticulum in the antral circular muscle of guinea pig stomach.

The present study was aimed at elucidating the mode of inhibitory action of tricyclic antidepressants on the smooth muscle. Effects of amitriptyline on the isolated detrusor muscle strips of the urinary bladder of the rabbit were examined. The spontaneous rhythmic movement of the muscle preparation was frequently observed, which was decreased or abolished by addition of amitriptyline $(10^{-5}{\sim}10^{-3}\;M)$. The muscle preparation responded with contraction dose dependently to carbachol, of which dose response curve shifted to the right in the presence of either amitriptyline or atropine. However, amitriptyline produced a nonparallel shift, whereas atropine caused a parallel one. In calcium free medium, the contraction response to carbachol was markedly decreased, which was resumed by the addition of $CaCl_2$ (2.5mM), but not in the presence of either amitriptyline or nifedipine. KCI (60 mM) produced a potent contraction, which was abolished in the presence of amitriptyline or nifedipine. These results suggest that amitriptyline, unlike atropine, not only acts as a noncompetitive antagonist at cholinergic muscarine receptors but also inhibits Ca-influx through the muscle cell membrane.

The purpose of this study is to obtain the effective concentration of capsaicin to relieve pain with no change in the number of C-fibers and its effective duration for pain relief. Capsaicin has been used extremely as a experimental tool and as topical medications for acute or chronic tissue injuries and partial nerve injury is the main cause of causalgiform pain disorders in humans. Here, the left sciatic nerve was ligated unilaterally at the high level of the thigh to prepare an animal model of this pain condition. The rat developed guarding behavior of the ipsilateral hind paw within a few hours after the operation and this behavior was maintained for several months thereafter, suggesting the possibility of spontaneous pain. These animals were divided into two groups(4-week & 8-week) and each group was subdivided into five groups by different concentration (0.05, 0.1, 0.5, 1.0 & 2.0%). Each capsaicin concentration was treated locally on the spinal cord-side of the ligated nerve and the foot withdrawal latency was measured. Thereafter, the dorsal roots of L5 were removed from both sides immediately after in tracardial perfusion for the counting of C-fibers by the histological procedure. There were no significant differences in the foot-withdrawal latency and the number of C-fibers between the left side treated with 0.05% capsaicin and the right side treated with the vehicle. However, latencies of the left sides treated with 0.1, 0.5, and 1.0% capsaicin increased significantly throughout 4-6 weeks with almost no change in the number of C-fibers, and the latencies showed the trends to approach slowly to those of the conditions after operation. The latency of subgroup treated with 2.0% increased by approximate 10% more than that of the right side throughout 8 weeks, and the number of C-fibers decreased by about 30% or more These results suggest that the elevated latency with capsaicin(0.1-1.0%) treatment is due to the inhibition of impulse transmission throughout the primary afferent fiber and the data from 2.0% are due to partial destruction of C-fibers. Therefore, capsaicin concentrations from 0.1% to 1.0% are probably very effective for the treatment of causalgiform pain with almost no destruction of C-fibers.

In urethane anesthetized cats, each vestibular semicircular canal nerve was electrically stimulated, and reflex responses of the cervical extensor and flexor (the splenius capitis and sternomastoid muscles) were recorded by means of electromyography. Stimulation of a unilateral (anterior, horizontal or posterior) canal nerve elicited excitation of the contralateral cervical muscles and inhibition of the ipsilateral ones; during the canal nerve stimulation, the two muscles in one side of the neck revealed synergistic responses. Based on these experimental results, we formulated a diagram showing the functional connections between the vestibular semicircular canals and the cervical muscles in the vestibulocollic reflex.

The present study was designed to evaluate effects of intermittent electrical stimulation of the sciatic nerve on the atrophic response of antigravity muscles, such as the soleus (slow m.) and medial gastrocnemius (fast m.) muscles. Rats (Sprague-Dawley, 245-255g) were subjected to a hindlimb suspension and divided into three groups : one was with hindlimb suspension (MS) and another with hindlimb suspension plus intermittent electrical stimulation of the sciatic nerve (HS ES). Control group (CONT) was kept free without strain of the hindlimb. After 7 days of hindlimb suspension, the soleus and medial gastrocnemius muscles were cut at their insertion sites, and were then connected to the force transducer to observe their mechanical properties. Optimal pulse width and frequency of electrical stimulation were 0.2ms, 20Hz for the soleus muscle and 0.3ms, 40Hz for the medial gastrocnemius muscle under supramaximal stimulation. Body weight and circumference of the hindlimb were significantly decreased in HS and HS-ES groups compared with the control group. In HS-ES group, however, the weight of the soleus muscle was not different from that in the control group while the weight of the medial gastrocnemius muscle was lower than that in the control group. In HS group, mechanical properties of muscle contraction including contraction time, half relaxation time, twitch tension, tetanic tension, and fatigue index of both muscles were significantly decreased compared with the control group except for twitch tension and tetanic tension of medial gastrocnemius muscle. The degree of atrophy of the soleus muscle in HS group was more prominent than that of the medial gastrocnemius muscle. Twitch tension and fatigue index of the soleus muscle and fatigue index of the medial gastrocnemius muscle in HS-ES group were not different from those of the control group. While mechanical properties of the soleus muscle examined were all significantly increased in HS-ES group compared with HS group, only contraction time and fatigue index of the medial gastrocnemius muscle were significantly increased in HS-ES group. These data indicate that intermittent electrical stimulation may be useful in prevention of muscle atrophy.