Pharmacological modulation of electromechanical coupling in the proximal and distal regions of the guinea-pig renal pelvis.
1. The effect of drugs affecting calcium and potassium channels and intracellular calcium handling/release on electromechanical coupling in the smooth muscle of the guinea-pig proximal vs. distal renal pelvis were investigated by using the single sucrose gap method. 2. Spontaneous action potentials discharged from the proximal renal pelvis were bell-shaped, did not show a pronounced plateau and had a small after-hyperpolarization. Spontaneous action potentials from the distal renal pelvis were characterized by a fast depolarization, a pronounced plateau and after-hyperpolarization. 3. Nifedipine (1 microM) suppressed action potentials in both regions of the renal pelvis. A submaximally effective concentration of nifedipine (50 nM) shortened action potential duration and reduced contractility in both regions of the renal pelvis. On the other hand Bay K 8644 (1 microM) markedly prolonged the duration of the action potential and increased contractility in both regions of the renal pelvis. 4. Tetraethylammonium (0.5 mM) markedly prolonged the action potential duration and contraction in the distal renal pelvis without affecting action potentials in the proximal renal pelvis. Similar effects were produced by a slightly higher concentration of tetraethylammonium (2 mM) in the proximal renal pelvis. 5. Charybdotoxin (30 nM) markedly prolonged the duration of action potential and increased and prolonged the contraction in both the proximal and distal renal pelvis. 6. 4-aminopyridine (1 mM) selectively increased the frequency of action potentials in the distal renal pelvis without affecting other parameters of the action potential nor contractility. 4-aminopyridine had no effect in the proximal renal pelvis. 7. The inhibitor of sarcoplasmic reticulum Ca-ATPase, cyclopiazonic acid (10 microM) transiently increased the frequency of action potentials in both regions of the renal pelvis; CPA markedly delayed the repolarizing phase of the action potential in both the proximal and distal renal pelvis and, in parallel, increased contractility. 8. We conclude that action potentials generated from the proximal and distal regions of the guinea-pig renal pelvis are evenly dependent upon the availability of L-type Ca channels; that Ca-dependent maxi K channels provide a major contribution to the repolarization of action potentials in both regions of the renal pelvis, thus regulating duration/intensity of Ca influx and contraction; that release of Ca from the internal store is not important in providing activator Ca for contraction but regulates duration of the action potential and may be involved in setting the frequency of discharge of pacemaker cells.
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Pharmacology Department, Menarini Richercha S.p.a, Florence, Italy.
Maggi
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D018999:Charybdotoxin / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D007682:Kidney Pelvis / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015761:4-Aminopyridine; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; C000543:cyclopiazonic acid