Specificity in the Interaction of HVA Ca²⁺Channel Types With Ca²⁺-Dependent AHPs and Firing Behavior in Neocortical Pyramidal Neurons

Abstract

Intracellular recordings and organic and inorganic Ca2+ channel blockers were used in a neocortical brain slice preparation to test whether high-voltage-activated (HVA) Ca2+ channels are differentially coupled to Ca2+-dependent afterhyperpolarizations (AHPs) in sensorimotor neocortical pyramidal neurons. For the most part, spike repolarization was not Ca2+ dependent in these cells, although the final phase of repolarization (after the fast AHP) was sensitive to block of N-type current. Between 30 and 60% of the medium afterhyperpolarization (mAHP) and between approximately 80 and 90% of the slow AHP (sAHP) were Ca2+ dependent. Based on the effects of specific organic Ca2+ channel blockers (dihydropyridines, omega-conotoxin GVIA, omega-agatoxin IVA, and omega-conotoxin MVIIC), the sAHP is coupled to N-, P-, and Q-type currents. P-type currents were coupled to the mAHP. L-type current was not involved in the generation of either AHP but (with other HVA currents) contributes to the inward currents that regulate interspike intervals during repetitive firing. These data suggest different functional consequences for modulation of Ca2+ current subtypes.

Control of Spontaneous Firing Patterns by the Selective Coupling of Calcium Currents to Calcium-Activated Potassium Currents in Striatal Cholinergic Interneurons

“…The sAHP current is activated by calcium entry through Ca v 1 (L-type) channels, the mAHP current through SK channels is activated by calcium entry through and Ca v 2.2 (N-type) channels, and the contribution of the BK currents to spike repolarization is activated by calcium influx through Ca v 2.1 channels (apparently of the Q type). Each of these examples of specific coupling can be found individually in other neurons (Viana et al, 1993;Tanabe et al, 1998), but the rules of preferential coupling of calcium channels to AHPs are, in general, diverse and cell-type specific (Viana et al, 1993;Sah, 1995;Williams et al, 1997;Marrion and Tavalin, 1998;Pineda et al, 1998;Shah and Haylett, 2000;Vilchis et al, 2000;Cloues and Sather, 2003). Studying this selectivity in cholinergic interneurons provides a unique opportunity to probe the context in which it is played out (i.e., in modulating the ongoing firing patterns exhibited by these neurons).…”

“…In several cell types, BK and SK potassium channels are coupled selectively to the various calcium channels (Viana et al, 1993;Sah, 1995;Williams et al, 1997;Marrion and Tavalin, 1998;Pineda et al, 1998;Cloues and Sather, 2003). Therefore, we sought to identify which calcium channels were responsible for the influx needed to activate the mAHP current.…”

“…In pyramidal cells, repolarization of action potentials, similar to cholinergic interneurons (Bennett et al, 2000), results from a potassium current through large-conductance calcium-activated potassium (BK) channels (Lancaster and Adams, 1986;Lancaster and Nicoll, 1987); mAHPs are generated by SK currents (Schwindt et al, 1988); and the calcium-dependent component of the sAHP that follows long trains of action potentials (Hotson and Prince, 1980;Gustafsson and Wigstrom, 1983;Schwindt et al, 1988) results from a potassium current that has yet to be identified (Sah and Faber, 2002;Vogalis et al, 2003). These calcium-dependent potassium currents rely on calcium entry through high-voltage-activated calcium channels (Viana et al, 1993;Sah, 1995;Williams et al, 1997;Pineda et al, 1998;Cloues and Sather, 2003). Several such cal-cium channels have been shown to contribute to barium currents recorded from dissociated cholinergic interneurons (Yan and Surmeier, 1996).…”

“…Several such cal-cium channels have been shown to contribute to barium currents recorded from dissociated cholinergic interneurons (Yan and Surmeier, 1996). One possible function for a diversity of calcium currents is the selective coupling of these channels to calciumdependent potassium channels (Viana et al, 1993;Sah, 1995;Williams et al, 1997;Marrion and Tavalin, 1998;Pineda et al, 1998;Shah and Haylett, 2000;Vilchis et al, 2000;Cloues and Sather, 2003). Because the calcium currents in cholinergic interneurons are targets of neuromodulation (Yan and Surmeier, 1996;Yan et al, 1997;Song et al, 2000;Pisani et al, 2002), finding such a selective coupling would provide a possible mechanism by which the firing patterns and the cholinergic output of these neurons are controlled by neuromodulators.…”

Specific Kinetic Alterations of Human CaV2.1 Calcium Channels Produced by Mutation S218L Causing Familial Hemiplegic Migraine and Delayed Cerebral Edema and Coma after Minor Head Trauma

“…Ca V 2.1 channels are located at presynaptic terminals and somatodendritic membranes (4) and are expressed in all brain structures that have been implicated in the pathogenesis of migraine (5). They play a prominent role in controlling neurotransmitter release (6) and also exert postsynaptic effects, such as on neuronal excitability (7).…”