Effects of dopamine and noradrenaline on Ca channels of cultured sensory and sympathetic neurons of chick

Abstract

The effects of noradrenaline and dopamine on voltage-dependent Ca currents were investigated in cultured dorsal root and sympathetic ganglion neurons from chick embryos. At concentrations of 1 to 10 microM, bath application of the neurotransmitters caused a general depression of inward Ca currents. Above -20 mV the decrease of the current amplitude was reversible and accompanied by a 2-10-fold prolongation of the activation time course. Below -20 mV, where a low voltage-activated Ca component is turned on, the size of the currents was reduced by 40% with little effect on the time course. Despite extensive wash-out, little sign of reversibility was observed in this case. Single-channel current recording in outside-out membrane patches revealed that at low membrane potentials dopamine and noradrenaline reversibly reduced single Ca-channel activity. This finding supports the view that in sensory and sympathetic neurons, both neurotransmitters affect the membrane conductance by modulating Ca permeability and not by activating catecholamine-specific channels able to carry transient outward currents. The probability of Ca channel opening is strongly reduced by addition of 10 microM of either catecholamine to the bath. The possible involvement of a voltage-dependent block of Ca channels by the neurotransmitters is discussed.

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

“…It closely resembles the one mediated by the G i ␤␥ subunit and associated to most G protein-coupled receptors [41] (see [35] for a review). The main effect of this "membrane-delimited" modulation is a delayed Ca 2+ channel activation at low voltages, which accelerates at higher potentials [42,43]. The slow activation derives from a prolonged latency of first channel opening [44] and is fully recovered by applying strong positive prepulses [45].…”

Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel α 1A subunit

“…Voltage-dependent inactivation of L-type Ca 2ϩ channels containing cloned ␣ 1C is slower than inactivation of P͞Q-type Ca 2ϩ channels containing cloned ␣ 1A expressed with the same auxiliary subunits in Xenopus oocytes (5,6). In addition, N-type and P͞Q-type Ca 2ϩ channels, but not L-type Ca 2ϩ channels, are modulated by neurotransmitter receptors acting through pertussis toxin-sensitive G proteins via membrane-delimited pathways that cause a positive shift in the voltage dependence of channel activation which is reversed by strong depolarization (9)(10)(11)(12). This modulatory effect is mediated by G protein ␤␥ subunits (13,14), possibly through direct binding to the Ca 2ϩ channel.…”

Role of the D 2 dopamine receptor in molecular adaptation to chronic hypoxia in PC12 cells

“…Several studies suggest that G i/o proteins are involved in the D 2 -mediated modulation of I Ca in various cell types [12,27,30]. In the current studies, PC12 cells were pretreated overnight with 200 ng/ml PTX, which inactivates G i and G o proteins.…”

“…Growing evidence strongly implicates G o rather than G i in this regulation, which could also affect the suppression of neurotransmitter release that is mediated by receptors on presynaptic neurons [4,7,8,28]. Furthermore, membrane-delimited G protein regulation of I Ca by DA has been shown in chick sensory and sympathetic neurons [27]. In addition, a study of rat anterior pituitary cells has shown that the G o α is primarily responsible for the inhibition of Ca 2+ currents induced by D 2 receptor activation [25].…”

“…The mechanism that couples the D 2 receptor to Ca 2+ channels is not well understood, but several studies point to the involvement of G i/o proteins that are sensitive to pertussin toxin (PTX) [12,16,27,36]. We know that PC12 cells adapt to prolonged exposure to hypoxia with a series of events such as increased responsiveness to acute exposure to hypoxia [5,23,34] and increased tyrosine hydroxylase gene expression [6,30].…”