Cyclic GMP modulates calcium currents in neurons of rabbit vesical parasympathetic ganglia

Cyclic GMP modulates calcium currents in neurons of rabbit vesical parasympathetic ganglia

S133 ~-ADRENERGIC RECEPTOR STIMULATION INDUCES Na+-DEPENDENT INWARD CURRENTS IN ACUTELY DISSOCIATED SPINAL MOTONEURONS. SATOMI ADACHI*' , JUN-ICHIRO ...

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S133

~-ADRENERGIC RECEPTOR STIMULATION INDUCES Na+-DEPENDENT INWARD CURRENTS IN ACUTELY DISSOCIATED SPINAL MOTONEURONS. SATOMI ADACHI*' , JUN-ICHIRO OKA', TAEU NAGAO*' AND HIDEOMI FUKUDA=, 'Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sclences, The University of Tokyo, Tokyo 113, 2Department of Pharmacology, Colle~e of Pharmacy, Nlhon University, Chlba 274, Japan. We reported that adrenaline depolarizes the membrane potential of m0t0neur0ns acutel~ dissociated from adult frog spinal cord, and that the effects are mediated by suppression of K currents and induction of inward currents through stimulation of a I- and ~-adrenerglc receptors, respectively (Adachl et ai.,1989). In the present study, we investigated the ionic components underlying the adrenallne-lnduced inward currents. The amplitude of adrenallne-lnduced currents were larger in hyperp01arlzed membrane potentials and decreased to zero in the depolarized membrane potentials higher than -30 mV. Adrenallne-lnduced currents did not reverse in the range FROG

of membrane p o t e n t i a l s t e s t e d , while g l u t a m a t e - i n d u c e d c u r r e n t s r e v e r s e d a t 0 mV, s u g g e s t i n g t h e n o n - s p e c i f i c c a t i o n c u r r e n t s a r e n o t i n v o l v e d In a d r e n a l i n e - l n d u c e d c u r r e n t s . A d r e n a l i n e - i n d u c e d c u r r e n t s were n o t a f f e c t e d by COC12, t e t r o d o t o x l n or m a n i p u l a t i o n of t h e e x t r a c e l l u l a r C1c o n c e n t r a t i o n . On t h e o t h e r hand, the a m p l i t u d e of a d r e n a l i n e - i n d u c e d c u r r e n t s was dependent on the extracellular Na ÷ c o n c e n t r a t i o n . These r e s u l t s I n d i c a t e t h a t a d r e n a l i n e I n d u c e s Na +d e p e n d e n t inward c u r r e n t s . 8-Br-chHP and f o r s k o l l n I n d u c e d inward c u r r e n t s w i t h s i m i l a r I-Y r e l a t l o n s h i p s and dependency on e x t r a c e l l u l a r Na* c o n c e n t r a t i o n t o a d r e n a l i n e - i n d u c e d c u r r e n t s . In c o n c l u s i o n , a d r e n a l i n e Induces Na+-dependent i n w a r d c u r r e n t s i n motoneurons by s t i m u l a t i o n of ~ - a d r e n e r g i c r e c e p t o r s presumably t h r o u g h a cMIP-mediated pathway.

CYCLIC GMP MODULATES CALCIUM CURRENTS IN NEURONS OF RABBIT VESICAL PARASYMPATHETIC GANGLIA. TAKASHI AKASU AND TOSHIHIKO NISHIMURA, Department of Physiolosy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830, Japan. Voltage-clamp recordings were made from neurons in rabbit vesical parasympathetic ganglia. Bath-appllcation of dibutyryl 3',5'-cyclic monophosphate (db-cyclic CMP, 10-100 ~M) caused a concentration-dependent, transient inward current followed by a long-lasting outward current. Membrane conductance was increased and decreased during the inward and outward currents, respectively. The cyclic GMP-indueed inward current was depressed in nominally calcium-free solutions, by cobalt (I mM) and nicardipine (I0 ~M). The mean reversal potential of the inward current was +42 mV and -20 mV in the presence and absence of calcium in the external solution, respectively. The db-cyclic G}~-induced inward current was not altered by lowering the external sodium concentration, raising external potassium concentration or by intracellular injection of caesium. A calcium-lnsensitive component of the db-cyclic GMP-Induced current was increased by lowering the external chloride concentration and blocked by SITS, a chloride channel blocker. Voltage-dependent transient and sustained calcium currents were depressed (primarily N-type) during the db-cyclie G}~-induced inward current and facilitated (primarily L-type) during the outward current. An impermeable analogue, cyclic CMP, was 30 times less potent than db-cyclic GMP. It is concluded that intracellular cyclic GMP causes not only activation of resting calcium and chloride channels but also a transient depression followed by long-lasting facilitation of voltage-dependent calcium currents in neurons of vesical parasympathetic ganglia.

Effect of Arachidonic Acid on K current of Rat Cerebe] lar Purkinje Cells. HIROSHI T A K & G I "x ETSURO I T O ~z , T O H R U YOSHIOgA x ,HARUHIHO BITO ~m . T~KAO SHIMIZU 2 . and YOUSUKE SEVAMA "2 ISchool of Human Sciences, Wnseda University, Mika,jima, Tokoro~nwa 359, ~Faculty of Medicine. The University of Tokyo. Honso Bunkyo-ku. Tokyo ]13. Japan. Arachidonic acid(Ah) is k n o w n to enhance K current of heart muscle cells. We examined the effect o f h A on t h e P u r k i n j e cells of rat cerebellar slices. Using a whole-cell patch clamp technique, we recorded the K current from single Purkinje cells in r a t cerebellar slices. This K current was reversibly enhanced by 10pM of hA but not by other fatty acids such as IinoJeic acid. stearic acid, or oleic acid. The effect of hA on K current decreased when the ce [ is were treated with indomethacin(lOpM) or NDGA(]OpM) which are known to be inhibitors for AA metabolism. These findings suggested that AA metabolltes enhance K current of Purkinje cell intracellurslly. In o r d e r to e l u c i d a t e the modulatory mechanism of AA on g channel, we measured the intracellular Ca concentration of Purkinje cells using the fura-2 system when it w ~ s s t i m u l a t e d b y AA. It w a s found that AA(10~M) increased the intraccllular Ca concentration in the Purkinje cells. Further study is n e e d e d to e l u c i d a t e the significance of Ca mobilization in the modulatory mechanism of K channel b y AA.