KEY POINTS: The @entity1 pineal gland is a neuroendocrine organ that responds to circadian and seasonal rhythms. Its major function is to secrete @entity2493 as a hormonal night signal in response to nocturnal delivery of @entity1063 from sympathetic neurons. Culturing @entity35 pinealocytes in @entity1063 for 24  h induced a low-voltage activated transient @entity141 current whose pharmacology and kinetics corresponded to a @entity3895 3.1 T-type channel. The upregulation of the T-type @entity141 current is initiated by b-adrenergic receptors, @entity1919 and @entity1919 -dependent protein kinase. Messenger RNA for @entity3895 3.1 T-type channels is significantly elevated by @entity1063 at 8  h and 24  h. The @entity1063 -induced T-type channel mediated an increased @entity141 entry and supported modest transient electrical responses to depolarizing stimuli, revealing the potential for circadian regulation of pinealocyte electrical excitability and @entity141 signalling. ABSTRACT: Our basic hypothesis is that @entity1 pinealocytes have cycling electrical excitability and @entity141 signalling that may contribute to the circadian rhythm of pineal @entity2493 secretion. This study asked whether the functional expression of voltage-gated @entity141 channels ( @entity3895 channels) in @entity35 pinealocytes is changed by culturing them in @entity1063 (NA) as a surrogate for the night signal. Channel activity was assayed as ionic currents under patch clamp and as optical signals from a @entity141 -sensitive dye. Channel mRNAs were assayed by quantitative polymerase chain reaction. Cultured without NA, pinealocytes showed only non-inactivating L-type @entity7236 -sensitive @entity141 current. After 24  h in NA, additional low-voltage activated transient @entity141 current developed whose pharmacology and kinetics corresponded to a T-type @entity3895 3.1 channel. This change was initiated by b-adrenergic receptors, @entity1919 and protein kinase A as revealed by pharmacological experiments. mRNA for @entity3895 3.1 T-type channels became significantly elevated, but mRNA for another T-type channel and for the major L-type channel did not change. After only 8  h of NA treatment, the @entity3895 3.1  mRNA was already elevated, but the transient @entity141 current was not. Even a 16  h wait without NA following the 8  h NA treatment induced little additional transient current. However, these cells were somehow primed to make transient current as a second NA exposure for only 60  min sufficed to induce large T-type currents. The NA-induced T-type channel mediated an increased @entity141 entry during short depolarizations and supported modest transient electrical responses to depolarizing stimuli. Such experiments reveal the potential for circadian regulation of excitability.

@entity1063 upregulates T-type calcium channels in XXXX pinealocytes.

@entity1 :: ('9606', 'Species') :: ['mammalian'] @entity7236 :: ('MESH:C038806', 'Chemical') :: ['dihydropyridine'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity2493 :: ('MESH:D008550', 'Chemical') :: ['melatonin'] @entity1919 :: ('MESH:D000242', 'Chemical') :: ['cyclic AMP'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['noradrenaline'] @entity3895 :: ('10537', 'Species') :: ['CaV']
@entity35 :: (10116,Species) :: ['rat']
