Calcium current activated by muscarinic receptors and thapsigargin in neuronal cells.

Abstract

The activation of muscarinic receptors in NIE-115 neuroblastoma cells elicits a voltage-independent calcium current. The current turns on slowly, reaches its maximum value ~ 45 s after applying the agonist, is sustained as long as agonist is present, and recovers by one half in ~ 10 s after washing the agonist away. The current density is 0.11 -+ 0.08 pA/pF (mean -+ SD; n = 12). It is absent in zero-Ca ++ saline and reduced by Mn ++ and Ba ++. The I(V) curve characterizing the current has an extrapolated reversal potential > +40 mV. The calcium current is observed in cells heavily loaded with BAPTA indicating that the calcium entry pathway is not directly gated by calcium. In fura-2 experiments, we find that muscarinic activation causes an elevation of intracellular Ca ++ that is due to both intracellular calcium release and calcium influx. The component of the signal that requires external Ca ++ has the same time course as the receptor operated calcium current. Calcium influx measured in this way elevates (Ca++)i by 89 -41 nM (n --7). Thapsigargin, an inhibitor of Ca++/ATPase associated with the endoplasmic reticulum (ER), activates a calcium current with similar properties. The current density is 0.22 ---0.20 pA/pF (n --6). Thapsigargin activated current is reduced by Mn ++ and Ba ++ and increased by elevated external Ca ++. Calcium influx activated by thapsigargin elevates (Ca++)i by 82 -+ 35 nM. The Ca ++ currents due to agonist and due to thapsigargin do not sum, indicating that these procedures activate the same process. Carbachol and thapsigargin both cause calcium release from internal stores and the calcium current bears strong similarity to calcium-release-activated calcium currents in nonexcitable cells (Hoth, M., and R.

Balancing Arc Synthesis, mRNA Decay, and Proteasomal Degradation

“…As a consequence, calcium accumulates at high concentrations in the cytosol (58,60,61). Consistent with calcium sensitivity of the Arc promoter (62), thapsigargin pretreatment increased Cch-induced Arc mRNA expression by ϳ50% (Fig.…”

Modulation of Ca2+ and K+ permeabilities by oxotremorine‐m (Oxo‐m) in rodent pancreatic B‐cells

“…Similar currents have been observed following the application of muscarinic agonists in excitable cells (Mathes & Thompson, 1994). 1C1RAC gating represents the most widely distributed voltage-independent Ca2+ entry mechanism, i.e.…”

Muscarinic and nicotinic receptors raise intracellular Ca2+ levels in rat carotid body type I cells.

“…B, peak elevations of [Ca2+]i in response to methacholine (n = 8) or muscarine (n = 4) from twelve independent experiments identical to that described in A. (Marley, 1988), where it is dependent on protein phosphorylation (Hemmings, Nairn, McGuinness, Huganir & Greengard, 1989 (Putney, 1990) and also recently in neuroblastoma (Mathes & Thompson, 1994) and cerebellar granule cells (Simpson, Challis & Nahorski, 1995). Additionally, muscarinic receptors might cause cell membrane depolarization, thus evoking Ca2P influx (Caulfield, 1993).…”