Regulation of Cation Channel Voltage and Ca²⁺ Dependence by Multiple Modulators

Abstract

Ion channel regulation is key to controlling neuronal excitability. However, the extent that modulators and gating factors interact to regulate channels is less clear. For Aplysia, a nonselective cation channel plays an essential role in reproduction by driving an afterdischarge in the bag cell neurons to elicit egg-laying hormone secretion. We examined the regulation of cation channel voltage and Ca2+ dependence by protein kinase C (PKC) and inositol trisphosphate (IP3)-two prominent afterdischarge signals. In excised, inside-out patches, the channel remained open longer and reopened more often with depolarization from -90 to +30 mV. As previously reported, PKC could closely associate with the channel and increase activity at -60 mV. We now show that, following the effects of PKC, voltage dependence was shifted to the left (essentially enhanced), particularly at more negative voltages. Conversely, the voltage dependence of channels lacking PKC was shifted to the right (essentially suppressed). Predictably, activity was increased at all Ca2+ concentrations following the effects of PKC; nevertheless, Ca2+ dependence was actually shifted to the right. Moreover, whereas IP3 did not alter activity at -60 mV, it drastically shifted Ca2+ dependence to the right-an outcome largely reversed by PKC. With respect to the afterdischarge, these data suggest PKC initially upregulates the channel by direct gating and shifting voltage dependence to the left. Subsequently, PKC and IP3 attenuate the channel by suppressing Ca2+ dependence. This ensures hormone delivery by allowing afterdischarge initiation and maintenance but also prevents interminable bursting. Similar regulatory interactions may be used by other neurons to achieve diverse outputs.

Diacylglycerol‐mediated regulation of Aplysia bag cell neuron excitability requires protein kinase C

“…B , upper), and the area above I OAG was down 50%. Previous work from our lab suggests that one of the non‐selective cation channels active during the afterdischarge is similar to the TRPM subfamily (Lupinsky & Magoski, ; Gardam & Magoski, ). Hence, we introduced a so‐called TRPM4‐specific inhibitor, 9‐phenanthrol (9‐Pt) (Grand et al .…”

“…Several non‐selective cation channels, including those from bag cell neurons, are Ca 2+ permeable (Lupinsky & Magoski, ; Gardam & Magoski, ; Geiger et al . ; Hickey et al .…”

“…In bag cell neurons, a key conductance that maintains the afterdischarge is a Ca 2+ ‐ and voltage‐dependent cation channel, which is modulated by calmodulin and PKC (Wilson et al . ; Magoski & Kaczmarek, ; Lupinsky & Magoski, ; Gardam & Magoski, ). These characteristics have also been attributed to TRPM4 and M5 channels (Launay et al .…”

“…; Sawada et al . ) or modulating cation channels (Gardam & Magoski, ). However, there is currently no information about the effects of DAG in this system.…”

Input-output signal processing plasticity of vagal motorneurons in response to cardiac ischemic injury

“…Further, the combination of norepinephrine and ANP likely works on post ganglionic neurons in the heart to mediate sympathoinhitibiton that was once thought to require input from at least two different neurons [54][55][56] , but we now show may plausibly come from the same vagal preganglionic neurons. There are several receptor and ion channels whose expression is increased and whose coordinated effects would lead to increased excitability and release of peptide transmitters [57][58][59][60][61] . There is also a shift from high expression of Rgs2 in other neurons to higher Rgs3 expression.…”