Modulators of internal Ca2+ stores and the spontaneous electrical and contractile activity of the guinea‐pig renal pelvis

Abstract

The role of internal Ca²⁺ stores in the generation of the rhythmic electrical and contractile activity in the guinea‐pig proximal renal pelvis was examined using intracellular microelectrode and muscle tension recording techniques. Ryanodine (30 μM) transiently increased contraction amplitude, while caffeine (0.5 – 3 mM) reduced contraction amplitude and frequency. Contractility was also reduced by 2‐aminoethoxy‐diphenylborate (2‐APB 60 μM), xestospongin C (1 μM), U73122 (5 μM) and neomycin (4 mM), blockers of IP₃‐dependent release from Ca²⁺ stores. 60 mM K⁺ saline‐evoked contractions were reduced by caffeine (1 mM), U73122 (5 μM) and neomycin (4 mM), but little affected by ryanodine or 2‐APB (60 μM). Spontaneous action potentials consisting of an initial spike followed by a long plateau were recorded (frequency 8.6±1.0 min⁻¹) in small urothelium‐denuded strips of proximal renal pelvis. Action potential discharge was blocked in 75 and 35% of cells by 2‐APB (60 μM) and caffeine (1 mM), respectively. In the remaining cells, only a truncation of the plateau phase was observed. Cyclopiazonic acid (CPA 10 μM for 10 – 180 min), blocker of CaATPase, transiently increased contraction frequency and amplitude. Action potential durations were increased 3.6 fold. Contraction amplitude and frequency slowly declined during a prolonged (>60 min) CPA exposure. We conclude that the action potential in caffeine‐sensitive cells and the shoulder component of caffeine‐insensitive action potential arise from the entry of Ca²⁺ through Ca²⁺ channels. The inhibitory actions of modulators of internal Ca²⁺ release were partially explained by a blockade of Ca²⁺ entry. British Journal of Pharmacology (2002) 135, 1363–1374; doi:10.1038/sj.bjp.0704609