Abstract

Here, we present the first study on the effects of compounds that interfere with calcium (Ca²⁺) handling by the endoplasmic reticulum (ER) and mitochondria on amperometrically measured quantal catecholamine release from single adrenal chromaffin cells of control and spontaneously hypertensive rats (SHRs). Acetylcholine (ACh) or K⁺ pulses triggered spike bursts of secretion by Ca²⁺ entry through Ca²⁺ channels. ER Ca²⁺ release triggered by a mixture of caffeine, ryanodine, and thapsigargin (CRT) or carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) (a mitochondrial protonophore) also caused bursts of secretory spikes. The spike bursts generated by ACh, K⁺, CRT, and FCCP were 3 to 4 times longer in SHRs compared with control cells; furthermore, the individual spikes were faster and had 3-fold greater quantal size. In additional experiments, a 90-s treatment was made with CRT or FCCP to block Ca²⁺ handling by the ER and mitochondria. In these conditions, the integrated spike burst responses elicited by ACh and K⁺ were potentiated 2- to 3-fold in control and SHR cells. This suggests that variations in Ca²⁺ entry and its subsequent redistribution into the ER and mitochondria are not responsible for the greater secretion seen in SHRs compared with control cells; rather, such differences seem to be due to greater quantal content of spike bursts and to greater quantal size of individual amperometric events.