HYPEROSMOTIC REGULATION OF VOLTAGE-GATED CALCIUM CURRENTS IN RAT ANTERIOR-PITUITARY-CELLS

1. The sensitivity of voltage-gated calcium currents to hyperosmotic m edia containing mannitol or sucrose (373-723 mOsm) and to the dihydrop yridine (DHP) calcium channel agonist Bay K 8644 was examined in enric hed populations of rat anterior pituitary somatotrophs by using the wh ole cell mode of the patch-clamp technique. 2. Hyperosmotic media redu ced the amplitude of voltage-gated calcium currents. With a 61.9% incr ease in extracellular medium osmolarity (523 mOsm), low voltage-activa ted (LVA) calcium currents were reduced to 67.9 +/- 17.8% of control s ize and high voltage-activated (HVA) calcium currents were reduced to 57.0 +/- 5.7% (mean +/- SD) of control size. The hyperosmotic suppress ion of HVA calcium currents was usually accompanied with a negative sh ift of 6.0 +/- 2.9 mV (mean +/- SD) in the activation curve of HVA cur rents. 3. The DHP calcium-channel agonist Bay K 8644 (10 mu M), which stimulates hormone secretion from somatotrophs, increased the amplitud e of HVA calcium currents to 212.6 +/- 67.2% of their control size, pr olonged their tail currents, and negatively shifted the activation cur ve of HVA calcium currents by 6.2 +/- 2.8 mV. 4. Hyperosmotic media re duced the amplitude of DHP-sensitive HVA calcium currents and their as sociated prolonged tail currents, thus providing direct evidence for h yperosmotic suppression of DHP-sensitive currents. 5. Hence, exposure of pituitary cells to hyperosmotic media reduced voltage-sensitive cal cium influx through LVA and DHP-sensitive HVA calcium channels. The in hibition of calcium influx through DHP-sensitive channels, which are i mplicated in regulation of hormone secretion in these cells, suggests that inhibitory hyperosmotic effects on hormone secretion from pituita ry cells may stem from inhibition of calcium influx, before the exocyt otic process. These results may also be relevant to effects of hyperto nicity on neurosecretion in the nervous system.