The contribution of voltage-gated Ca currents to K channel activation during ovine adrenal chromaffin cell development

Prior to the development of adrenal innervation, the adrenal medulla is capable of responding to low blood oxygen directly. However, this response is lost once adrenal innervation is established. Previous work by our group has outlined mechanisms involved in this direct hypoxic response and the means by which innervation causes the loss of the direct hypoxic response in the ovine adrenal. The current study further investigates mechanisms which may underlie the developmental loss of the direct hypoxic response by concentrating on two aspects of cell function which regulate catecholamine secretion: the contribution of different types of Ca²⁺ channels to the total Ca²⁺ current and the contribution of each Ca²⁺ channel type to K⁺ channel activation. We identified that Ca²⁺ current size at −40 to −10 mV is increased in amplitude in fetal chromaffin cells. This is not due to the increased prevalence or size of T-type Ca²⁺ currents present at these voltages. The relative contribution of L-, N- or P/Q-type Ca²⁺ channels to total Ca²⁺ current and to activation of the K⁺ current is unchanged during chromaffin cell development, however K⁺ current density increases with age. Our results indicate that there is a developmental shift in relative expression of T-type, but not L-, N- or P/Q-type, Ca²⁺ channels in ovine chromaffin cells. The increased K⁺ current density in adult cells may result in an altered response to an equal stimulus, while larger Ca²⁺ current at negative voltages in fetal cells may facilitate Ca²⁺ entry and catecholamine secretion in response to small depolarisations such as those induced by hypoxia.