Na⁺/Ca²⁺ exchange and its role in intracellular Ca²⁺ regulation in guinea pig detrusor smooth muscle

The role of Na(+)/Ca(2+) exchange in regulating intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated smooth muscle cells from the guinea pig urinary bladder was investigated. Incremental reduction of extracellular Na(+) concentration resulted in a graded rise of [Ca(2+)](i); 50-100 microM strophanthidin also increased [Ca(2+)](i). A small outward current accompanied the rise of [Ca(2+)](i) in low-Na(+) solutions (17.1 +/- 1.8 pA in 29.4 mM Na(+)). The quantity of Ca(2+) influx through the exchanger was estimated from the charge carried by the outward current and was approximately 30 times that which is necessary to account for the rise of [Ca(2+)](i), after correction was made for intracellular Ca(2+) buffering. Ca(2+) influx through the exchanger was able to load intracellular Ca(2+) stores. It is concluded that the level of resting [Ca(2+)](i) is not determined by the exchanger, and under resting conditions (membrane potential -50 to -60 mV), there is little net flux through the exchanger. However, a small rise of intracellular Na(+) concentration would be sufficient to generate significant net Ca(2+) influx.