AJP - Cell Physiology, Vol 265, Issue 4 C1030-C1036, Copyright © 1993 by American Physiological Society
Temporal patterns of alpha 1-receptor stimulation regulate amplitude and frequency of calcium transients
C. Schofl, G. Brabant, R. D. Hesch, A. von zur Muhlen, P. H. Cobbold and K. S. Cuthbertson
Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, Germany.
The pulsatile release of neurotransmitters and many hormones might encode
specific biological information according to temporal pattern. We tested
this hypothesis by applying pulsed alpha 1-adrenoceptor stimulation to
single aequorin-injected hepatocytes. The amplitude of free Ca2+ transients
induced by rapid phenylephrine pulses (20-s interpulse interval) and
continuous stimulation was similar (approximately 640 nM) but increased to
approximately 1,000 nM as the interpulse interval was increased to 120 s.
The same overall response was maintained despite a 13-fold reduction in
average phenylephrine concentration. Some regimes of pulsed phenylephrine
stimulation could give a higher frequency of pulsed phenylephrine
stimulation could give a higher frequency of free calcium oscillations than
continuous stimulation, or more rapid stimulation when some agonist pulses
failed to elicit a free Ca2+ transient. For the same average phenylephrine
concentration (0.3-0.6 microM), pulsed regimes could result in
significantly higher frequencies and integrated responses than constant
application. The lags between phenylephrine pulses and free Ca2+ transients
reduced as the period between pulses increased. The amplitude and lag data
are consistent with a refractory period of 18 s and a recovery phase with a
time constant of approximately 100 s, perhaps corresponding to
dephosphorylation of alpha 1-adrenoceptors phosphorylated by protein kinase
C during each free Ca2+ transient.
