Parathyroid hormone enhances calcium current in snail neurones--simulation of the effect by phorbol esters.
Effects of parathyroid hormone substance (PTH) on the voltage-activated calcium current (ICa) were studied on intracellularly perfused neurones of the snail, Helix pomatia, under voltage-clamp conditions. Application of 0.1 nM PTH produced a marked potentiation of the current. The effect developed slowly (60-70 min) and remained after removal of PTH. Potentiation could be observed in most neurones, but varied considerably from cell to cell; in some neurones ICa was increased 2- to 3-fold. Addition of ethylenebis(oxonitrilo)tetraacetate (EGTA, 10 mM) to, or removal of adenosine 5'-triphosphate (ATP, 2 mM) from the intracellular perfusing solution resulted in a suppression or attenuation of the potentiating effect. The effect could be reproduced by the synthetic 1-34 amino acid fragment of PTH. Extracellularly applied protein kinase-C (PK-C) activator phorbol ester phorbol 12-myristate 13-acetate (PMA, 0.1-10 microM) produced a similar slow increase in ICa (up to 1.5- to 2-fold), while its inactive analogue (4 alpha-phorbol ester) had no effect on ICa. The effects of PTH and PMA were not additive. PK-C inhibitors [1-(5-isoquinoline-sulphonyl)-2-methylpiperazine hydrochloride] (H-7, 100 microM) and staurosporine (100 microM) as well as calcium channel antagonists Cd2+, verapamil, nifedipine and nimodipine depressed the effect of PTH. The chloride channel blocker 4,4'-diisothiocyanato-stilbene-2,2'-disulphonic acid (DIDS, 1 mM) did not affect the potentiating action of PTH. Activation of the adenylate cyclase system also potentiated ICa in some neurones, but this effect had a different time course and was additive to the effect of PTH.2=
Kostyuk
P G
PG
A.A. Bogomoletz Institute of Physiology, Ukrainian Academy of Sciences, Kiev.
Lukyanetz
E A
EA
Ter-Markosyan
A S
AS
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology; D004357:Drug Synergism; D006372:Helix, Snails; D007424:Intracellular Fluid / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015220:Calcium Channels; D010281:Parathyroid Hormone; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate